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Sample records for alter glucose utilization

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

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    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.

  2. Anterior-posterior and lateral hemispheric alterations in cortical glucose utilization in Alzheimer's disease

    International Nuclear Information System (INIS)

    Friedland, T.F.; Budinger, T.F.; Jaqust, W.J.; Yano, Y.; Huesman, R.H.; Knittel, B.; Koss, E.; Ober, B.A.

    1984-01-01

    The anatomical and chemical features of Alzheimer's disease (AD) are not distributed evenly throughout the brain. However, the nature of this focality has not been well established in vivo. Dynamic studies using the Donner 280-Crystal Positron Tomograph with (F-18)2-fluorodeoxyglucose were performed in 17 subjects meeting current research criteria for AD, and in 7 healthy age-matched control subjects. Glucose metabolic rates in the temporal-parietal cortex are 27% lower in AD than in controls. Ratios of activity density reveal consistently lower metabolic rates in temporal-parietal than frontal cortex in the AD group, while healthy aged subjects have equal metabolic rates in the two areas. Similar findings have been reported by other laboratories. A major finding is a striking lateral asymmetry of cortical metabolism in AD which does not favor either hemisphere. (The asymmetry is 13% in the AD group, 3% in controls, p<.005.) This has not been previously reported in AD. The consistency with which anterior-posterior metabolic differences are found in AD suggests that the focality of the metabolic changes may be used to develop a noninvasive diagnostic test for the disorder. The metabolic asymmetry in AD may be compared to the clinical and pathological asymmetry found in Creutzfeldt-Jakob disease, and may represent an additional link between AD and the subacute spongiform encephalopathies

  3. 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

  4. Anterior-posterior and lateral hemispheric alterations in cortical glucose utilization in Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Friedland, T.F.; Budinger, T.F.; Jaqust, W.J.; Yano, Y.; Huesman, R.H.; Knittel, B.; Koss, E.; Ober, B.A.

    1984-01-01

    The anatomical and chemical features of Alzheimer's disease (AD) are not distributed evenly throughout the brain. However, the nature of this focality has not been well established in vivo. Dynamic studies using the Donner 280-Crystal Positron Tomograph with (F-18)2-fluorodeoxyglucose were performed in 17 subjects meeting current research criteria for AD, and in 7 healthy age-matched control subjects. Glucose metabolic rates in the temporal-parietal cortex are 27% lower in AD than in controls. Ratios of activity density reveal consistently lower metabolic rates in temporal-parietal than frontal cortex in the AD group, while healthy aged subjects have equal metabolic rates in the two areas. Similar findings have been reported by other laboratories. A major finding is a striking lateral asymmetry of cortical metabolism in AD which does not favor either hemisphere. (The asymmetry is 13% in the AD group, 3% in controls, p<.005.) This has not been previously reported in AD. The consistency with which anterior-posterior metabolic differences are found in AD suggests that the focality of the metabolic changes may be used to develop a noninvasive diagnostic test for the disorder. The metabolic asymmetry in AD may be compared to the clinical and pathological asymmetry found in Creutzfeldt-Jakob disease, and may represent an additional link between AD and the subacute spongiform encephalopathies.

  5. Restraint Stress Impairs Glucose Homeostasis Through Altered ...

    African Journals Online (AJOL)

    olayemitoyin

    Summary: The study investigated the potential alteration in the level of insulin and adiponectin, as well as the expression of insulin receptors (INSR) and glucose transporter 4 GLUT-4 in chronic restraint stress rats. Sprague-Dawley rats were randomly divided into two groups: the control group and stress group in which the ...

  6. 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)

  7. Ketosis proportionately spares glucose utilization in brain.

    Science.gov (United States)

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

    2013-08-01

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

  8. Regional alterations in glucose consumption and metabolite levels during postischemic recovery in cat brain.

    Science.gov (United States)

    Tanaka, K; Welsh, F A; Greenberg, J H; O'Flynn, R; Harris, V A; Reivich, M

    1985-12-01

    Local CMRgl (LCMRgl) and metabolite levels were measured in the same tissue samples following 4 h of recirculation after 1 h of occlusion of the middle cerebral artery in the cat. The rate of glucose utilization was calculated using direct measurement of tissue deoxyglucose-6-phosphate and using a "lumped" constant corrected in each sample for alterations in tissue glucose. Increased LCMRgl (compared with that in sham-operated animals) occurred in regions with only minor alterations in levels of lactate and phosphocreatine. By contrast, LCMRgl was markedly depressed in regions with major changes in lactate and high-energy phosphates. Interestingly, tissue levels of glucose and unphosphorylated deoxyglucose were abnormally elevated in regions with profound energy failure. These results indicate an inhibition of glucose utilization in regions damaged by ischemia, despite the persistent elevation of tissue lactate. Increased glucose metabolism at 4 h post ischemia was detected only in areas with minor anaerobic alteration of metabolite levels.

  9. 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

  10. Effect of anesthesia on glucose production and utilization in rats

    International Nuclear Information System (INIS)

    Penicaud, L.; Ferre, P.; Kande, J.; Leturque, A.; Issad, T.; Girard, J.

    1987-01-01

    This study was undertaken to determine the effects of pentobarbital anesthesia (50 mg/kg ip) on glucose kinetics and individual tissue glucose utilization in vivo, in chronically catheterized rats. Glucose turnover studies were carried out using [3- 3 H] glucose as tracer. A transient hyperglycemia and an increased glucose production were observed 3 min after induction of anesthesia. However, 40 min after induction of anesthesia, glycemia returned to the level observed in awake animals, whereas glucose turnover was decreased by 30% as compared with unanesthetized rats. These results are discussed with regard to the variations observed in plasma insulin, glucagon, and catecholamine levels. Glucose utilization by individual tissues was studied by the 2-[1- 3 H] deoxyglucose technique. A four- to fivefold decrease in glucose utilization was observed in postural muscles (soleus and adductor longus), while in other nonpostural muscles (epitrochlearis, tibialis anterior, extensor digitorum longus, and diaphragm) and other tissues (white and brown adipose tissues) anesthesia did not modify the rate of glucose utilization. A decrease in glucose utilization was also observed in the brain

  11. Effect of anesthesia on glucose production and utilization in rats

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    Penicaud, L.; Ferre, P.; Kande, J.; Leturque, A.; Issad, T.; Girard, J.

    1987-03-01

    This study was undertaken to determine the effects of pentobarbital anesthesia (50 mg/kg ip) on glucose kinetics and individual tissue glucose utilization in vivo, in chronically catheterized rats. Glucose turnover studies were carried out using (3-/sup 3/H) glucose as tracer. A transient hyperglycemia and an increased glucose production were observed 3 min after induction of anesthesia. However, 40 min after induction of anesthesia, glycemia returned to the level observed in awake animals, whereas glucose turnover was decreased by 30% as compared with unanesthetized rats. These results are discussed with regard to the variations observed in plasma insulin, glucagon, and catecholamine levels. Glucose utilization by individual tissues was studied by the 2-(1-/sup 3/H) deoxyglucose technique. A four- to fivefold decrease in glucose utilization was observed in postural muscles (soleus and adductor longus), while in other nonpostural muscles (epitrochlearis, tibialis anterior, extensor digitorum longus, and diaphragm) and other tissues (white and brown adipose tissues) anesthesia did not modify the rate of glucose utilization. A decrease in glucose utilization was also observed in the brain.

  12. Glucose utilization rates regulate intake levels of artificial sweeteners.

    Science.gov (United States)

    Tellez, Luis A; Ren, Xueying; Han, Wenfei; Medina, Sara; Ferreira, Jozélia G; Yeckel, Catherine W; de Araujo, Ivan E

    2013-11-15

    It is well established that animals including humans attribute greater reinforcing value to glucose-containing sugars compared to their non-caloric counterparts, generally termed 'artificial sweeteners'. However, much remains to be determined regarding the physiological signals and brain systems mediating the attribution of greater reinforcing value to sweet solutions that contain glucose. Here we show that disruption of glucose utilization in mice produces an enduring inhibitory effect on artificial sweetener intake, an effect that did not depend on sweetness perception or aversion. Indeed, such an effect was not observed in mice presented with a less palatable, yet caloric, glucose solution. Consistently, hungry mice shifted their preferences away from artificial sweeteners and in favour of glucose after experiencing glucose in a hungry state. Glucose intake was found to produce significantly greater levels of dopamine efflux compared to artificial sweetener in dorsal striatum, whereas disrupting glucose oxidation suppressed dorsal striatum dopamine efflux. Conversely, inhibiting striatal dopamine receptor signalling during glucose intake in sweet-naïve animals resulted in reduced, artificial sweetener-like intake of glucose during subsequent gluco-deprivation. Our results demonstrate that glucose oxidation controls intake levels of sweet tastants by modulating extracellular dopamine levels in dorsal striatum, and suggest that glucose utilization is one critical physiological signal involved in the control of goal-directed sweetener intake.

  13. Renal gluconeogenesis and increased glucose utilization in shock.

    Science.gov (United States)

    Archer, L T; Benjamin, B; Lane, M M; Hinshaw, L B

    1976-09-01

    The roles of renal gluconeogenesis and glucose utilization in control, hemorrhaged, and endotoxin-injected animals were investigated using anesthetized, eviscerated, nonnephrectomized and nephrectomized dogs. Results demonstrate an increased glucose utilization in both hemorrhagic and endotoxic shock which was marked after endotoxin. Since blood glucose values dropped more in nephrectomized, hemorrhaged animals, in contrast to the nonnephrectomized, hemorrhaged dogs, the kidneys were assumed to perform a significant gluconeogenic role. The kidneys did not appear to perform gluconeogenesis in endotoxin shock since blood glucose levels were comparable in eviscerated, endotoxin-treated animals whether nephrectomized or not. To ascertain the tissue responsible for the increased glucose utilization in endotoxin shock, a study was performed with endotoxin added to blood in vitro (estimated LD100 concentration). The endotoxin-treated blood (n = 7) demonstrated an increased glucose utilization compared with saline controls (n = 7) (P less than or equal 0.02). Acclerated glucose utilization rates were comparable between the eviscerated, nephrectomized animals and in vitro experiments. These data suggest that excessive glucose demand by certain blood components may partially explain the lethal hypoglycemia of endotoxin shock.

  14. Pancreatic islets of variable size - insulin secretion and glucose utilization

    International Nuclear Information System (INIS)

    Colella, R.M.; Bonner-Weir, S.; Braunstein, L.P.; Schwalke, M.; Weir, G.C.

    1985-01-01

    Glucose metabolism and insulin secretion were studied in isolated rat pacreatic islets of different sizes and the amount of tissue was quantitated by the measurement of DNA. It was found that larger islets (140-210 ng DNA/islet) utilized more glucose (based on the conversion of 3 H-5-glucose to 3 H 2 O) per ng of DNA than islets containing less DNA (60-120 ng/islet). However, the insulin secreted per ng of DNA in response to a given glucose concentration was the same in islets of all sizes. Also, the islet insulin and glucagon content when expressed in terms of DNA did not depend upon islet size. Thus, although glucose utilization rates expressed as a function of islet DNA content were greater in larger islets, no such relationship was found for glucose-induced insulin release or insulin and glucagon content. 17 reference, 1 figure, 3 tables

  15. Glucose utilization and anti-oxidative mechanisms of the aqueous ...

    African Journals Online (AJOL)

    olayemitoyin

    In a previous study, HU was hypothesized to regulate glucose homeostasis via enhanced peripheral glucose utilization in experimental models of DM (Adeneye and Adeyemi,. 2009a; Adeneye and Adeyemi, 2009b). Unfortunately, till date there has not been any study further investigating the exact mechanism by which.

  16. Restraint stress impairs glucose homeostasis through altered insulin ...

    African Journals Online (AJOL)

    The study investigated the potential alteration in the level of insulin and adiponectin, as well as the expression of insulin receptors (INSR) and glucose transporter 4 GLUT-4 in chronic restraint stress rats. Sprague-Dawley rats were randomly divided into two groups: the control group and stress group in which the rats were ...

  17. Alterations in glucose kinetics induced by pentobarbital anesthesia

    International Nuclear Information System (INIS)

    Lang, C.H.; Bagby, G.J.; Hargrove, D.M.; Hyde, P.M.; Spitzer, J.J.

    1987-01-01

    Because pentobarbital is often used in investigations related to carbohydrate metabolism, the in vivo effect of this drug on glucose homeostasis was studied. Glucose kinetics assessed by the constant intravenous infusion of [6- 3 H]- and [U- 14 C]glucose, were determined in three groups of catheterized fasted rats: conscious, anesthetized and body temperature maintained, and anesthetized but body temperature not maintained. After induction of anesthesia, marked hypothermia developed in rats not provided with external heat. Anesthetized rats that developed hypothermia showed a decrease in mean arterial blood pressure (25%) and heart rate (40%). Likewise, the plasma lactate concentration and the rates of glucose appearance, recycling, and metabolic clearance were reduced by 30-50% in the hypothermic anesthetized rats. Changes in whole-body carbohydrate metabolism were prevented when body temperature was maintained. Because plasma pentobarbital levels were similar between the euthermic and hypothermic rats during the first 2 h of the experiment, the rapid reduction in glucose metabolism in this latter group appears related to the decrease in body temperature. The continuous infusion of epinephrine produced alterations in glucose kinetics that were not different between conscious animals and anesthetized rats with body temperature maintained. Thus pentobarbital-anesthetized rats became hypothermic when kept at room temperature and exhibited marked decreases in glucose metabolism. Such changes were absent when body temperature was maintained during anesthesia

  18. Corticosterone and exogenous glucose alter blood glucose levels, neurotoxicity, and vascular toxicity produced by methamphetamine.

    Science.gov (United States)

    Bowyer, John F; Tranter, Karen M; Sarkar, Sumit; George, Nysia I; Hanig, Joseph P; Kelly, Kimberly A; Michalovicz, Lindsay T; Miller, Diane B; O'Callaghan, James P

    2017-10-01

    Our previous studies have raised the possibility that altered blood glucose levels may influence and/or be predictive of methamphetamine (METH) neurotoxicity. This study evaluated the effects of exogenous glucose and corticosterone (CORT) pretreatment alone or in combination with METH on blood glucose levels and the neural and vascular toxicity produced. METH exposure consisted of four sequential injections of 5, 7.5, 10, and 10 mg/kg (2 h between injections) D-METH. The three groups given METH in combination with saline, glucose (METH+Glucose), or CORT (METH+CORT) had significantly higher glucose levels compared to the corresponding treatment groups without METH except at 3 h after the last injection. At this last time point, the METH and METH+Glucose groups had lower levels than the non-METH groups, while the METH+CORT group did not. CORT alone or glucose alone did not significantly increase blood glucose. Mortality rates for the METH+CORT (40%) and METH+Glucose (44%) groups were substantially higher than the METH (glucose during METH exposure increases lethality and may exacerbate neurodegeneration. Neuroinflammation, specifically microglial activation, was associated with degenerating neurons in the parietal cortex and thalamus after METH exposure. The activated microglia in the parietal cortex were surrounding vasculature in most cases and the extent of microglial activation was exacerbated by CORT pretreatment. Our findings show that acute CORT exposure and elevated blood glucose levels can exacerbate METH-induced vascular damage, neuroinflammation, neurodegeneration and lethality. Cover Image for this issue: doi. 10.1111/jnc.13819. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  19. Effect of insulin on in vivo glucose utilization in individual tissues of anesthetized lactating rats

    International Nuclear Information System (INIS)

    Burnol, A.F.; Ferre, P.; Leturque, A.; Girard, J.

    1987-01-01

    Glucose utilization rate has been measured in skeletal muscles, white adipose tissue, and mammary gland of anesthetized nonlactating and lactating rats. During lactation, basal [1- 3 H] glucose utilization is decreased by 40% in periovarian white adipose tissue and by 65% in epitrochlearis and extensor digitorum longus but not in soleus muscle. This may be related to the lower blood glucose and plasma insulin concentrations observed during lactation. Basal glucose utilization rate in the mammary gland was, respectively, 18 +/- 2 and 350 +/- 50 μg/min in nonlactating and lactating rats. During the euglycemic hyperinsulinemic clamp, a physiological increment in plasma insulin concentration induces a similar increase in glucose utilization rate in skeletal muscles and white adipose tissue in the two groups of rats. Furthermore this low increase in plasma insulin concentration does not alter mammary glucose utilization rate in nonlactating rats but induces the same increase as a maximal insulin concentration in lactating rats. These data show that the active mammary gland is the most insulin-sensitive tissue of the lactating rat that has been tested. The overall increase in insulin sensitivity and responsiveness that has been described in lactating rats can then mainly be attributed to the presence of the active mammary gland. Plasma insulin was determined by radioimmunoassay

  20. Effect of insulin on in vivo glucose utilization in individual tissues of anesthetized lactating rats

    Energy Technology Data Exchange (ETDEWEB)

    Burnol, A.F.; Ferre, P.; Leturque, A.; Girard, J.

    1987-02-01

    Glucose utilization rate has been measured in skeletal muscles, white adipose tissue, and mammary gland of anesthetized nonlactating and lactating rats. During lactation, basal (1-TH) glucose utilization is decreased by 40% in periovarian white adipose tissue and by 65% in epitrochlearis and extensor digitorum longus but not in soleus muscle. This may be related to the lower blood glucose and plasma insulin concentrations observed during lactation. Basal glucose utilization rate in the mammary gland was, respectively, 18 +/- 2 and 350 +/- 50 g/min in nonlactating and lactating rats. During the euglycemic hyperinsulinemic clamp, a physiological increment in plasma insulin concentration induces a similar increase in glucose utilization rate in skeletal muscles and white adipose tissue in the two groups of rats. Furthermore this low increase in plasma insulin concentration does not alter mammary glucose utilization rate in nonlactating rats but induces the same increase as a maximal insulin concentration in lactating rats. These data show that the active mammary gland is the most insulin-sensitive tissue of the lactating rat that has been tested. The overall increase in insulin sensitivity and responsiveness that has been described in lactating rats can then mainly be attributed to the presence of the active mammary gland. Plasma insulin was determined by radioimmunoassay.

  1. Artificial sweeteners induce glucose intolerance by altering the gut microbiota.

    Science.gov (United States)

    Suez, Jotham; Korem, Tal; Zeevi, David; Zilberman-Schapira, Gili; Thaiss, Christoph A; Maza, Ori; Israeli, David; Zmora, Niv; Gilad, Shlomit; Weinberger, Adina; Kuperman, Yael; Harmelin, Alon; Kolodkin-Gal, Ilana; Shapiro, Hagit; Halpern, Zamir; Segal, Eran; Elinav, Eran

    2014-10-09

    Non-caloric artificial sweeteners (NAS) are among the most widely used food additives worldwide, regularly consumed by lean and obese individuals alike. NAS consumption is considered safe and beneficial owing to their low caloric content, yet supporting scientific data remain sparse and controversial. Here we demonstrate that consumption of commonly used NAS formulations drives the development of glucose intolerance through induction of compositional and functional alterations to the intestinal microbiota. These NAS-mediated deleterious metabolic effects are abrogated by antibiotic treatment, and are fully transferrable to germ-free mice upon faecal transplantation of microbiota configurations from NAS-consuming mice, or of microbiota anaerobically incubated in the presence of NAS. We identify NAS-altered microbial metabolic pathways that are linked to host susceptibility to metabolic disease, and demonstrate similar NAS-induced dysbiosis and glucose intolerance in healthy human subjects. Collectively, our results link NAS consumption, dysbiosis and metabolic abnormalities, thereby calling for a reassessment of massive NAS usage.

  2. Alteration of de novo glucose production contributes to fasting hypoglycaemia in Fyn deficient mice.

    Directory of Open Access Journals (Sweden)

    Yingjuan Yang

    Full Text Available Previous studies have demonstrated that glucose disposal is increased in the Fyn knockout (FynKO mice due to increased insulin sensitivity. FynKO mice also display fasting hypoglycaemia despite decreased insulin levels, which suggested that hepatic glucose production was unable to compensate for the increased basal glucose utilization. The present study investigates the basis for the reduction in plasma glucose levels and the reduced ability for the liver to produce glucose in response to gluconeogenic substrates. FynKO mice had a 5-fold reduction in phosphoenolpyruvate carboxykinase (PEPCK gene and protein expression and a marked reduction in pyruvate, pyruvate/lactate-stimulated glucose output. Remarkably, de novo glucose production was also blunted using gluconeogenic substrates that bypass the PEPCK step. Impaired conversion of glycerol to glucose was observed in both glycerol tolerance test and determination of the conversion of (13C-glycerol to glucose in the fasted state. α-glycerol phosphate levels were reduced but glycerol kinase protein expression levels were not changed. Fructose-driven glucose production was also diminished without alteration of fructokinase expression levels. The normal levels of dihydroxyacetone phosphate and glyceraldehyde-3-phosphate observed in the FynKO liver extracts suggested normal triose kinase function. Fructose-bisphosphate aldolase (aldolase mRNA or protein levels were normal in the Fyn-deficient livers, however, there was a large reduction in liver fructose-6-phosphate (30-fold and fructose-1,6-bisphosphate (7-fold levels as well as a reduction in glucose-6-phosphate (2-fold levels. These data suggest a mechanistic defect in the allosteric regulation of aldolase activity.

  3. Altered glucose metabolism in Harvey-ras transformed MCF10A cells.

    Science.gov (United States)

    Zheng, Wei; Tayyari, Fariba; Gowda, G A Nagana; Raftery, Daniel; McLamore, Eric S; Porterfield, D Marshall; Donkin, Shawn S; Bequette, Brian; Teegarden, Dorothy

    2015-02-01

    Metabolic reprogramming that alters the utilization of glucose including the "Warburg effect" is critical in the development of a tumorigenic phenotype. However, the effects of the Harvey-ras (H-ras) oncogene on cellular energy metabolism during mammary carcinogenesis are not known. The purpose of this study was to determine the effect of H-ras transformation on glucose metabolism using the untransformed MCF10A and H-ras oncogene transfected (MCF10A-ras) human breast epithelial cells, a model for early breast cancer progression. We measured the metabolite fluxes at the cell membrane by a selective micro-biosensor, [(13)C6 ]glucose flux by (13)C-mass isotopomer distribution analysis of media metabolites, intracellular metabolite levels by NMR, and gene expression of glucose metabolism enzymes by quantitative PCR. Results from these studies indicated that MCF10A-ras cells exhibited enhanced glycolytic activity and lactate production, decreased glucose flux through the tricarboxylic acid (TCA) cycle, as well as an increase in the utilization of glucose in the pentose phosphate pathway (PPP). These results provide evidence for a role of H-ras oncogene in the metabolic reprogramming of MCF10A cells during early mammary carcinogenesis. © 2013 Wiley Periodicals, Inc.

  4. Glucose And Hydrocarbon Utilization By Bacteria Isolated From ...

    African Journals Online (AJOL)

    Hydrocarbon utilizing bacteria were isolated from diesel impacted sites at the University of Port Harcourt using the vapour phase transfer method. The isolates were identified as Bacillus, Pseudomonas, Acinetobacter, Serratia, and Micrococcus species. Examination of cultures supplemented with glucose revealed that the ...

  5. Proline requirement for glucose utilization by Peptostreptococcus anaerobius ATCC 27337.

    Science.gov (United States)

    Curtis, M A; Wittenberger, C L; Thompson, J

    1987-02-01

    Resting cells of Peptostreptococcus anaerobius maintained under anaerobic conditions were unable to metabolize either glucose or alanine. The addition of proline to the appropriate suspension, however, resulted in the immediate utilization of both compounds. Fermentation of alanine by the cells required that stoichiometric concentrations of proline be present in the medium; and during the oxidation of alanine, proline was simultaneously reduced to the ring cleavage product delta-aminovaleric acid. Although proline was required to initiate glucose transport, stoichiometric amounts of the imino acid were not necessary for glucose fermentation. Proline also stimulated the uptake and concomitant phosphorylation of the nonmetabolizable glucose analog 2-deoxy-D-glucose. The proline requirement for glucose transport by P. anaerobius could be replaced by adding ferricyanide or simply by aerating the cell suspension. The initiation of sugar uptake by proline, ferricyanide, and O2 was attributed to the capacity of these compounds to function as electron acceptors, which permitted reoxidation of the (reduced) intracellular nucleotide pool and the formation (from an endogenous reserve) of the high-energy donor(s) required for the vectorial transport and phosphorylation of sugar.

  6. 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.

  7. The effect of altered gut flora on glucose intolerance in C57BL/6NTac mice

    DEFF Research Database (Denmark)

    Rune, Ida; Ellekilde, Merete; Hansen, Camilla Hartmann Friis

    Recent studies have shown that long term broad spectrum antibiotic treatment improves glucose tolerance in mice. We hypothesize that it is primarily in the early life that altering of the gut microbiota will have an impact on glucose intoleance.....

  8. The effect of altered gut flora on glucose intolerance in C57BL/6NTac mice

    DEFF Research Database (Denmark)

    Rune, Ida; Ellekilde, Merete; Hansen, Camilla Hartmann Friis

    Recent studies have shown that long term broad spectrum antibiotic treatment improves glucose tolerance in mice. We hypothesize that it is primarily in the early life that altering of the gut microbiota will have an impact on glucose intoleance........Recent studies have shown that long term broad spectrum antibiotic treatment improves glucose tolerance in mice. We hypothesize that it is primarily in the early life that altering of the gut microbiota will have an impact on glucose intoleance.....

  9. Rapid selection of glucose-utilizing variants of the polyhydroxyalkanoate producer Ralstonia eutropha H16 by incubation with high substrate levels.

    Science.gov (United States)

    Franz, A; Rehner, R; Kienle, A; Grammel, H

    2012-01-01

    The application of Ralstonia eutropha H16 for producing polyhydroxyalkanoates as bioplastics is limited by the incapability of the bacterium to utilize glucose as a growth substrate. This study aims in characterizing glucose-utilizing strains that arose after incubation with high glucose levels, in comparison with previously published mutants, generated either by mutagenesis or by metabolic engineering. Cultivations on solid and liquid media showed that the application of high substrate concentrations rapidly induced a glucose-positive phenotype. The time span until the onset of growth and the frequency of glucose-utilizing colonies were correlated to the initial glucose concentration. All mutants exhibited elevated activities of glucose-6-phosphate dehydrogenase. The glucose-positive phenotype was abolished after deleting genes for the N-acetylglucosamine phosphotransferase system. A procedure is provided for selecting glucose-utilizing R. eutropha H16 in an unprecedented short time period and without any mutagenic treatment. An altered N-acetylglucosamine phosphotransferase system appears to be a common motif in all glucose-utilizing mutants examined so far. The correlation of the applied glucose concentration and the appearance of glucose-utilizing mutants poses questions about the randomness or the specificity of adaptive mutations in general. Furthermore, glucose-adapted strains of R. eutropha H16 could be useful for the production of bioplastics. © 2011 The Authors. Letters in Applied Microbiology ©2011 The Society for Applied Microbiology.

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

    Directory of Open Access Journals (Sweden)

    Vijayalakshmi Varma

    2015-06-01

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

  11. Glucose predictability, blood capillary permeability, and glucose utilization rate in subcutaneous, skeletal muscle, and visceral fat tissues.

    Science.gov (United States)

    Koutny, Tomas

    2013-11-01

    This study suggests an approach for the comparison and evaluation of particular compartments with modest experimental setup costs. A glucose level prediction model was used to evaluate the compartment's glucose transport rate across the blood capillary membrane and the glucose utilization rate by the cells. The glucose levels of the blood, subcutaneous tissue, skeletal muscle tissue, and visceral fat were obtained in experiments conducted on hereditary hypertriglyceridemic rats. After the blood glucose level had undergone a rapid change, the experimenter attempted to reach a steady blood glucose level by manually correcting the glucose infusion rate and maintaining a constant insulin infusion rate. The interstitial fluid glucose levels of subcutaneous tissue, skeletal muscle tissue, and visceral fat were evaluated to determine the reaction delay compared with the change in the blood glucose level, the interstitial fluid glucose level predictability, the blood capillary permeability, the effect of the concentration gradient, and the glucose utilization rate. Based on these data, the glucose transport rate across the capillary membrane and the utilization rate in a particular tissue were determined. The rates obtained were successfully verified against positron emission tomography experiments. The subcutaneous tissue exhibits the lowest and the most predictable glucose utilization rate, whereas the skeletal muscle tissue has the greatest glucose utilization rate. In contrast, the visceral fat is the least predictable and has the shortest reaction delay compared with the change in the blood glucose level. The reaction delays obtained for the subcutaneous tissue and skeletal muscle tissue were found to be approximately equal using a metric based on the time required to reach half of the increase in the interstitial fluid glucose level. © 2013 Published by Elsevier Ltd.

  12. The rate of lactate production from glucose in hearts is not altered by per-deuteration of glucose

    Science.gov (United States)

    Funk, Alexander M.; Anderson, Brian L.; Wen, Xiaodong; Hever, Thomas; Khemtong, Chalermchai; Kovacs, Zoltan; Sherry, A. Dean; Malloy, Craig R.

    2017-11-01

    This study was designed to determine whether perdeuterated glucose experiences a kinetic isotope effect (KIE) as glucose passes through glycolysis and is further oxidized in the tricarboxylic acid (TCA) cycle. Metabolism of deuterated glucose was investigated in two groups of perfused rat hearts. The control group was supplied with a 1:1 mixture of [U-13C6]glucose and [1,6-13C2]glucose, while the experimental group received [U-13C6,U-2H7]glucose and [1,6-13C2]glucose. Tissue extracts were analyzed by 1H, 2H and proton-decoupled 13C NMR spectroscopy. Extensive 2H-13C scalar coupling plus chemical shift isotope effects were observed in the proton-decoupled 13C NMR spectra of lactate, alanine and glutamate. A small but measureable (∼8%) difference in the rate of conversion of [U-13C6]glucose vs. [1,6-13C2]glucose to lactate, likely reflecting rates of Csbnd C bond breakage in the aldolase reaction, but conversion of [U-13C6]glucose versus [U-13C6,U-2H7]glucose to lactate did not differ. This shows that the presence of deuterium in glucose does not alter glycolytic flux. However, there were two distinct effects of deuteration on metabolism of glucose to alanine and oxidation of glucose in the TCA. First, alanine undergoes extensive exchange of methyl deuterons with solvent protons in the alanine amino transferase reaction. Second, there is a substantial kinetic isotope effect in metabolism of [U-13C6,U-2H7]glucose to alanine and glutamate. In the presence of [U-13C6,U-2H7]glucose, alanine and lactate are not in rapid exchange with the same pool of pyruvate. These studies indicate that the appearance of hyperpolarized 13C-lactate from hyperpolarized [U-13C6,U-2H7]glucose is not substantially influenced by a deuterium kinetic isotope effect.

  13. Glucose Utilization and Production by the Dog Kidney In Vivo in Metabolic Acidosis and Alkalosis

    Science.gov (United States)

    Costello, J.; Scott, J. M.; Wilson, P.; Bourke, E.

    1973-01-01

    Using D-[1-14C]glucose as a tracer, renal glucose utilization and production was measured in chronic metabolic acidosis and alkalosis in dog kidney in vivo. In six experiments in acidosis, mean total renal glucose production was 4.447±1.655 SE μmol/min and glucose utilization was 4.187±0.576 SE μmol/min. In five alkalotic experiments it was found that mean total glucose production was 12.227±2.026 SE μmol/min and glucose utilization was 18.186±2.054 SE μmol/min. Renal glucose utilization and production are therefore significantly higher in alkalosis than in acidosis in vivo. Since glucose production is maximal under conditions when glutamine extraction is minimal (i.e. alkalosis), it is apparent that in alkalosis glutamine is not a major precursor of glucose. PMID:4685085

  14. Streptozotocin alters glucose transport, connexin expression and endoplasmic reticulum functions in neurons and astrocytes.

    Science.gov (United States)

    Biswas, Joyshree; Gupta, Sonam; Verma, Dinesh Kumar; Singh, Sarika

    2017-07-25

    The study was undertaken to explore the cell-specific streptozotocin (STZ)-induced mechanistic alterations. STZ-induced rodent model is a well-established experimental model of Alzheimer's disease (AD) and in our previous studies we have established it as an in vitro screening model of AD by employing N2A neuronal cells. Therefore, STZ was selected in the present study to understand the STZ-induced cell-specific alterations by utilizing neuronal N2A and astrocytes C6 cells. Both neuronal and astrocyte cells were treated with STZ at 10, 50, 100 and 1000μM concentrations for 48h. STZ exposure caused significant decline in cellular viability and augmented cytotoxicity of cells involving astrocytes activation. STZ treatment also disrupted the energy metabolism by altered glucose uptake and its transport in both cells as reflected with decreased expression of glucose transporters (GLUT) 1/3. The consequent decrease in ATP level and decreased mitochondrial membrane potential was also observed in both the cells. STZ caused increased intracellular calcium which could cause the initiation of endoplasmic reticulum (ER) stress. Significant upregulation of ER stress-related markers were observed in both cells after STZ treatment. The cellular communication of astrocytes and neurons was altered as reflected by increased expression of connexin 43 along with DNA fragmentation. STZ-induced apoptotic death was evaluated by elevated expression of caspase-3 and PI/Hoechst staining of cells. In conclusion, study showed that STZ exert alike biochemical alterations, ER stress and cellular apoptosis in both neuronal and astrocyte cells. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Sulforaphane induces adipocyte browning and promotes glucose and lipid utilization.

    Science.gov (United States)

    Zhang, Hui Q; Chen, Shi Y; Wang, An S; Yao, An J; Fu, Jian F; Zhao, Jin S; Chen, Fen; Zou, Zu Q; Zhang, Xiao H; Shan, Yu J; Bao, Yong P

    2016-10-01

    Obesity is closely related to the imbalance of white adipose tissue storing excess calories, and brown adipose tissue dissipating energy to produce heat in mammals. Recent studies revealed that acquisition of brown characteristics by white adipocytes, termed "browning," may positively contribute to cellular bioenergetics and metabolism homeostasis. The goal was to investigate the putative effects of natural antioxidant sulforaphane (1-isothiocyanate-4-methyl-sulfonyl butane; SFN) on browning of white adipocytes. 3T3-L1 mature white adipocytes were treated with SFN for 48 h, and then the mitochondrial content, function, and energy utilization were assessed. SFN was found to induce 3T3-L1 adipocytes browning based on the increased mitochondrial content and activity of respiratory chain enzymes, whereas the mechanism involved the upregulation of nuclear factor E2-related factor 2/sirtuin1/peroxisome proliferator activated receptor gamma coactivator 1 alpha signaling. SFN enhanced uncoupling protein 1 expression, a marker for brown adipocyte, leading to the decrease in cellular ATP. SFN also enhanced glucose uptake and oxidative utilization, lipolysis, and fatty acid oxidation in 3T3-L1 adipocytes. SFN-induced browning of white adipocytes enhanced the utilization of cellular fuel, and application of SFN is a promising strategy to combat obesity and obesity-related metabolic disorder. © 2016 The Authors. Molecular Nutrition & Food Research Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Efficacy of lower doses of vanadium in restoring altered glucose ...

    Indian Academy of Sciences (India)

    induced diabetic Wistar rats in lower doses in combination with Trigonella foenum graecum, a well-known hypoglycemic agent used in traditional Indian medicines. The effect of this combination was studied on lens morphology and glucose ...

  17. 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

  18. The effect of altered gut flora on glucose intolerance in C57BL/6NTac mice

    DEFF Research Database (Denmark)

    Rune, Ida; Hansen, Axel Jacob Kornerup; Ellekilde, Merete

    Background Recent studies have shown that long term broad spectrum antibiotic treatment improves glucose tolerance in mice. We hypothesize that it is primarily the early life altering of the gut microbiota, which will have an impact on glucose intolerance. Study setup 40 C57BL/6NTac mice were...

  19. In vivo glucose utilization in rat tissues during the three phases of starvation

    International Nuclear Information System (INIS)

    Cherel, Y.; Burnol, A.F.; Leturque, A.; Le Maho, Y.

    1988-01-01

    Three phases of starvation have been described from changes in protein and lipid utilization in birds and mammals. In the present study, tissue glucose utilization was measured in vivo during these three phases, using a 2-deoxy-[1-3H]glucose technique in the anesthetized rat. According to this technique, the term glucose utilization therefore refers to transport and phosphorylation of glucose in tissues, ie, whatever is the fate of glucose. Whole-body glucose turnover rate, which was determined by a continuous infusion of [3-3H]glucose, decreased by 40% during the first two days of starvation (phase 1); it did not change thereafter, neither in the protein-sparing phase 2 nor in phase 3, which is marked by an increase in net protein breakdown. Two days of starvation caused a marked decrease in the glucose utilization in skeletal muscles; this decrease was higher in oxidative muscles (65% in diaphragm, 66% in soleus) than in glycolytic muscles (31% in extensor digitorum longus, 34% in epitrochlearis). Glucose utilization also decreased in heart atria (75%), heart ventricles (93%), and white adipose tissue (54%); by contrast, there was a two-fold increase in glucose utilization in brown adipose tissue and no change in brain and skin. No variations were observed in glucose utilization in any of the tissues from phase 1 to phase 2. However, phase 3 was marked by a decrease in glucose utilization in extensor digitorum longus (45%), brown adipose tissue (76%), brain (29%), and skin (40%), whereas there was a 2.3- and 3.4-fold increase in glucose utilization in diaphragm and heart ventricles, respectively

  20. In vivo glucose utilization in rat tissues during the three phases of starvation

    Energy Technology Data Exchange (ETDEWEB)

    Cherel, Y.; Burnol, A.F.; Leturque, A.; Le Maho, Y.

    1988-11-01

    Three phases of starvation have been described from changes in protein and lipid utilization in birds and mammals. In the present study, tissue glucose utilization was measured in vivo during these three phases, using a 2-deoxy-(1-3H)glucose technique in the anesthetized rat. According to this technique, the term glucose utilization therefore refers to transport and phosphorylation of glucose in tissues, ie, whatever is the fate of glucose. Whole-body glucose turnover rate, which was determined by a continuous infusion of (3-3H)glucose, decreased by 40% during the first two days of starvation (phase 1); it did not change thereafter, neither in the protein-sparing phase 2 nor in phase 3, which is marked by an increase in net protein breakdown. Two days of starvation caused a marked decrease in the glucose utilization in skeletal muscles; this decrease was higher in oxidative muscles (65% in diaphragm, 66% in soleus) than in glycolytic muscles (31% in extensor digitorum longus, 34% in epitrochlearis). Glucose utilization also decreased in heart atria (75%), heart ventricles (93%), and white adipose tissue (54%); by contrast, there was a two-fold increase in glucose utilization in brown adipose tissue and no change in brain and skin. No variations were observed in glucose utilization in any of the tissues from phase 1 to phase 2. However, phase 3 was marked by a decrease in glucose utilization in extensor digitorum longus (45%), brown adipose tissue (76%), brain (29%), and skin (40%), whereas there was a 2.3- and 3.4-fold increase in glucose utilization in diaphragm and heart ventricles, respectively.

  1. Efficacy of lower doses of vanadium in restoring altered glucose ...

    Indian Academy of Sciences (India)

    Unknown

    doses in combination with Trigonella foenum graecum, a well-known hypoglycemic agent used in traditional. Indian medicines. The effect of this combination was studied on lens morphology and glucose metabolism in diabetic rats. Lens, an insulin-independent tissue, was found severely affected in diabetes showing visual ...

  2. The effect of altered gut flora on glucose intolerance in C57BL/6NTac mice

    DEFF Research Database (Denmark)

    Rune, Ida; Nielsen, Dennis Sandris; Hansen, Axel Jacob Kornerup

    Background Recent studies have shown that long term broad spectrum antibiotic treatment improves glucose tolerance in mice. We hypothesize that it is primarily the early life altering of the gut microbiota, which will have an impact on glucose intolerance. Study setup 40 C57BL/6NTac mice were...... no clustering was evident. Discussion Our results substantiate the theory implying an effect of gut microbiota on glucose tolerance. Furthermore, it seems evident that a window of opportunity for altering the host-microbial interaction response exists only in early life when host immunity is still developing...

  3. Pregnancy induces molecular alterations reflecting impaired insulin control over glucose oxidative pathways that only in women with a family history of Type 2 diabetes last beyond pregnancy.

    Science.gov (United States)

    Piccinini, M; Mostert, M; Seardo, M A; Bussolino, S; Alberto, G; Lupino, E; Ramondetti, C; Buccinnà, B; Rinaudo, M T

    2009-01-01

    In circulating lymphomonocytes (CLM) of patients with Type 2 diabetes (DM2) pyruvate dehydrogenase (PDH), the major determinant of glucose oxidative breakdown, is affected by a cohort of alterations reflecting impaired insulin stimulated glucose utilization. The cohort is also expressed, although incompletely, in 40% of healthy young subjects with a DM2-family history (FH). Pregnancy restrains glucose utilization in maternal peripheral tissues to satisfy fetal requirements. Here we explore whether pregnant women develop the PDH alterations and, if so, whether there are differences between women with and without FH (FH+, FH-). Ten FH+ and 10 FH- were evaluated during pregnancy (12-14, 24-26, and 37-39 weeks) and 1 yr after (follow-up) for fasting plasma glucose and insulin as well as body mass index (BMI), and for the PDH alterations. Twenty FH- and 20 FH+ non-pregnant women served as controls. All FH+ and FH- controls exhibited normal clinical parameters and 8 FH+ had an incomplete cohort of PDH alterations. In FH- and FH+ pregnant women at 12-14 weeks clinical parameters were normal; from 24-26 weeks, with unvaried glucose, insulin and BMI rose more in FH- and only in the latter recovered the 12-14 weeks values at follow-up. In all FH-, the cohort of PDH alterations was incomplete at 24-26 weeks, complete at 37-39 weeks, and absent at follow-up but complete from 12-14 weeks including follow-up in all FH+. In FH-, the cohort is an acquired trait restricted to pregnancy signaling transiently reduced insulin-stimulated glucose utilization; in FH+, instead, it unveils the existence of an inherited DM2-related background these women all have, that is awakened by pregnancy and as such lastingly impairs insulin-stimulated glucose utilization.

  4. Glucose ingestion during endurance training does not alter adaptation

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Fischer, Christian P; Plomgaard, Peter

    2009-01-01

    , 2) lower citrate synthase (CS) and beta-hydroxyacyl-CoA dehydrogenase (beta-HAD) activity and glycogen content in skeletal muscle, and 3) attenuated endurance performance enhancement in the trained state. To investigate this we studied nine male subjects who performed 10 wk of one-legged knee...... extensor training. They trained one leg while ingesting a 6% glucose solution (Glc) and ingested a sweetened placebo while training the other leg (Plc). The subjects trained their respective legs 2 h at a time on alternate days 5 days a week. Endurance training increased peak power (P(max)) and time...

  5. Utilization of dietary glucose in the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Alemany Marià

    2011-10-01

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

  6. Detecting alterations of glucose and lipid components in human serum by near-infrared Raman spectroscopy

    Directory of Open Access Journals (Sweden)

    Rita de Cássia Fernandes Borges

    Full Text Available Introduction Raman spectroscopy may become a tool for the analysis of glucose and triglycerides in human serum in real time. This study aimed to detect spectral differences in lipid and glucose components of human serum, thus evaluating the feasibility of Raman spectroscopy for diagnostic purposes. Methods A total of 44 samples of blood serum were collected from volunteers and submitted for clinical blood biochemical analysis. The concentrations of glucose, cholesterol, triglycerides, and low-density and high-density lipoproteins (LDL and HDL were obtained using standard biochemical assays. Serum samples were placed in Eppendorf tubes (200 µL, kept cooled (5 °C and analyzed with near-infrared Raman spectroscopy (830 nm, 250 mW, 50 s accumulation. The mean spectra of serum with normal or altered concentrations of each parameter were compared to determine which Raman bands were related to the differences between these two groups. Results Differences in peak intensities of altered sera compared to normal ones depended on the parameter under analysis: for glucose, peaks were related to glucose; for lipid compounds the main changes occurred in the peaks related to cholesterol, lipids (mainly triolein and proteins. Principal Components Analysis discriminated altered glucose, cholesterol and triglycerides from the normal serum based on the differences in the concentration of these compounds. Conclusion Differences in the peak intensities of selected Raman bands could be seen in normal and altered blood serum samples, and may be employed as a means of diagnosis in clinical analysis.

  7. Altered glucose kinetics in diabetic rats during Gram-negative infection

    International Nuclear Information System (INIS)

    Lang, C.H.; Dobrescu, C.; Bagby, G.J.; Spitzer, J.J.

    1987-01-01

    The present study examined the purported exacerbating effect of sepsis on glucose metabolism in diabetes. Diabetes was induced in rats by an intravenous injection of 70 or 45 mg/kg streptozotocin. The higher dose produced severe diabetes, whereas the lower dose of streptozotocin produced a miler, latent diabetes. After a chronic diabetic state had developed for 4 wk, rats had catheters implanted and sepsis induced by intraperitoneal injections of live Escherichia coli. After 24 h of sepsis the blood glucose concentration was unchanged in nondiabetics and latent diabetics, but glucose decreased from 15 to 8 mM in the septic severe diabetic group. This decrease in blood glucose was not accompanied by alterations in the plasma insulin concentration. Glucose turnover, assessed by the constant intravenous infusion of [6- 3 H]- and [U- 14 C]glucose, was elevated in the severe diabetic group, compared with either latent diabetics or nondiabetics. Sepsis increased the rate of glucose disappearance in nondiabetic rats but had no effect in either group of diabetic animals. Sepsis also failed to alter the insulinogenic index, used to estimate the insulin secretory capacity, in diabetic rats. Thus the present study suggests that the imposition of nonlethal Gram-negative sepsis on severe diabetic animals does not further impair glucose homeostasis and that the milder latent diabetes was not converted to a more severe diabetic state by the septic challenge

  8. Biocatalytic anode for glucose oxidation utilizing carbon nanotubes for direct electron transfer with glucose oxidase

    Energy Technology Data Exchange (ETDEWEB)

    Vaze, Abhay; Hussain, Nighat; Tang, Chi [Department of Chemistry, University of Connecticut, Storrs, CT 06269-3060 (United States); Leech, Donal [School of Chemistry, National University of Ireland, Galway (Ireland); Rusling, James [Department of Chemistry, University of Connecticut, Storrs, CT 06269-3060 (United States); Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06032 (United States); School of Chemistry, National University of Ireland, Galway (Ireland)

    2009-10-15

    Covalently linked layers of glucose oxidase, single-wall carbon nanotubes and poly-L-lysine on pyrolytic graphite resulted in a stable biofuel cell anode featuring direct electron transfer from the enzyme. Catalytic response observed upon addition of glucose was due to electrochemical oxidation of FADH{sub 2} under aerobic conditions. The electrode potential depended on glucose concentration. This system has essential attributes of an anode in a mediator-free biocatalytic fuel cell. (author)

  9. Efficacy of lower doses of vanadium in restoring altered glucose ...

    Indian Academy of Sciences (India)

    Unknown

    Insulin restored the levels of altered enzyme acti- vities and metabolites almost to control levels. Sodium orthovanadate (0⋅6 mg/ml) and Trigonella administered separately to diabetic animals could partially reverse the diabetic changes, metabolic and morphological, while vanadate in lowered dose in combination with ...

  10. 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.

  11. Regulation of glucose utilization and lipogenesis in adipose tissue ...

    Indian Academy of Sciences (India)

    Unknown

    Both insulin and manganese caused an increased oxidation of carbon-1 of glucose and an increase of its incorporation into 14C-lipids in ... of the importance of obesity to cardiovascular problems,. NIDDM and insulin resistance ... genesis in liver and adipose tissue caused by manganese treatment of rats fed a high fat diet ...

  12. Regulation of glucose utilization and lipogenesis in adipose tissue ...

    Indian Academy of Sciences (India)

    Unknown

    In order to evaluate the modulatory effects of manganese, high fat diet fed and alloxan diabetic rats were taken and the changes in the glucose oxidation, glycerol release and effects of manganese on these parameters were measured from adipose tissue. An insulin-mimetic effect of manganese was observed in the adipose ...

  13. Coordination of glucose and glutamine utilization by an expanded Myc network

    OpenAIRE

    Kaadige, Mohan R; Elgort, Marc G; Ayer, Donald E

    2010-01-01

    Glucose and glutamine are the most abundant circulating nutrients and support the growth and proliferation of all cells, in particular rapidly growing and dividing cancer cells. Several recent studies implicate an expanded Myc network in how cells sense and utilize both glucose and glutamine. These studies reveal an unappreciated coordination between glycolysis and glutaminolysis, potentially providing new targets for therapeutic intervention in cancer.

  14. 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.)

  15. 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.

  16. High glucose alters retinal astrocytes phenotype through increased production of inflammatory cytokines and oxidative stress.

    Directory of Open Access Journals (Sweden)

    Eui Seok Shin

    Full Text Available Astrocytes are macroglial cells that have a crucial role in development of the retinal vasculature and maintenance of the blood-retina-barrier (BRB. Diabetes affects the physiology and function of retinal vascular cells including astrocytes (AC leading to breakdown of BRB. However, the detailed cellular mechanisms leading to retinal AC dysfunction under high glucose conditions remain unclear. Here we show that high glucose conditions did not induce the apoptosis of retinal AC, but instead increased their rate of DNA synthesis and adhesion to extracellular matrix proteins. These alterations were associated with changes in intracellular signaling pathways involved in cell survival, migration and proliferation. High glucose conditions also affected the expression of inflammatory cytokines in retinal AC, activated NF-κB, and prevented their network formation on Matrigel. In addition, we showed that the attenuation of retinal AC migration under high glucose conditions, and capillary morphogenesis of retinal endothelial cells on Matrigel, was mediated through increased oxidative stress. Antioxidant proteins including heme oxygenase-1 and peroxiredoxin-2 levels were also increased in retinal AC under high glucose conditions through nuclear localization of transcription factor nuclear factor-erythroid 2-related factor-2. Together our results demonstrated that high glucose conditions alter the function of retinal AC by increased production of inflammatory cytokines and oxidative stress with significant impact on their proliferation, adhesion, and migration.

  17. Effects of hyperglycemia on glucose production and utilization in humans. Measurement with [3H]-2-, [3H]-3-, and [14C]-6-glucose

    International Nuclear Information System (INIS)

    Bell, P.M.; Firth, R.G.; Rizza, R.A.

    1986-01-01

    Studies with tritiated isotopes of glucose have demonstrated that hyperglycemia per se stimulates glucose utilization and suppresses glucose production in humans. These conclusions rely on the assumption that tritiated glucose provides an accurate measure of glucose turnover. However, if in the presence of hyperglycemia the isotope either loses its label during futile cycling or retains its label during cycling through glycogen, then this assumption is not valid. To examine this question, glucose utilization and glucose production rates were measured in nine normal subjects with a simultaneous infusion of [ 3 H]-2-glucose, an isotope that may undergo futile cycling but does not cycle through glycogen; [ 14 C]-6-glucose, an isotope that may cycle through glycogen but does not futile cycle; and [ 3 H]-3-glucose, an isotope that can both undergo futile cycling and cycle through glycogen. In the postabsorptive state at plasma glucose concentration of 95 mg X dl-1, glucose turnover determined with [ 14 C]-6-glucose (2.3 +/- 0.1 mg X kg-1 X min-1) was greater than that determined with [3 3 H]glucose (2.1 +/- 0.1 mg X kg-1 X min-1, P = 0.002) and slightly less than that determined with [ 3 H]-2-glucose (2.7 +/- 0.2 mg X kg-1 X min-1, P = 0.08). Plasma glucose was then raised from 95 to 135 to 175 mg X dl-1 while insulin secretion was inhibited, and circulating insulin, glucagon, and growth hormone concentrations were maintained constant by infusion of these hormones and somatostatin. Glucose production and utilization rates determined with [ 14 C]-6-glucose continued to be less than those determined with [ 3 H]-2-glucose and greater than those seen with [ 3 H]-3-glucose

  18. Progressive alterations in lipid and glucose metabolism during short-term fasting in young adult men

    NARCIS (Netherlands)

    Klein, S.; Sakurai, Y.; Romijn, J. A.; Carroll, R. M.

    1993-01-01

    Stable isotope tracers and indirect calorimetry were used to evaluate the progressive alterations in lipid and glucose metabolism after 12, 18, 24, 30, 42, 54, and 72 h of fasting in six healthy male volunteers. The rates of appearance (Ra) of glycerol and palmitic acid in plasma doubled from 2.08

  19. Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver

    Science.gov (United States)

    Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver D.B. Johnson, 1 W.O. Ward, 2 V.L. Bass, 2 M.C.J. Schladweiler, 2A.D. Ledbetter, 2 D. Andrews, and U.P. Kodavanti 2 1 Curriculum in Toxicology, UNC School of Medicine, Cha...

  20. Chromium supplementation alters both glucose and lipid metabolism in feedlot cattle during the receiving period

    Science.gov (United States)

    Crossbred steers (n = 20; 235 +/- 4 kg) were fed 53 days during a receiving period to determine if supplementing chromium (Cr; KemTRACE®brandChromium Propionate 0.04%, Kemin Industries) would alter the glucose or lipid metabolism of newly received cattle. Chromium premixes were supplemented to add 0...

  1. Chromium supplementation alters the glucose and lipid metabolism of feedlot cattle during the receiving period

    Science.gov (United States)

    Crossbreed steers (n = 20; 235 ± 4 kg) were fed 53 d during a receiving period to determine if supplementing chromium (Cr; KemTRACE®brand Chromium Propionate 0.04%, Kemin Industries) would alter the glucose or lipid metabolism of newly received cattle. Chromium premixes were supplemented to add 0 (C...

  2. The salivary microbiome is altered in the presence of a high salivary glucose concentration.

    Directory of Open Access Journals (Sweden)

    J Max Goodson

    Full Text Available Type II diabetes (T2D has been associated with changes in oral bacterial diversity and frequency. It is not known whether these changes are part of the etiology of T2D, or one of its effects.We measured the glucose concentration, bacterial counts, and relative frequencies of 42 bacterial species in whole saliva samples from 8,173 Kuwaiti adolescents (mean age 10.00 ± 0.67 years using DNA probe analysis. In addition, clinical data related to obesity, dental caries, and gingivitis were collected. Data were compared between adolescents with high salivary glucose (HSG; glucose concentration ≥ 1.0 mg/d, n = 175 and those with low salivary glucose (LSG, glucose concentration < 0.1 mg/dL n = 2,537.HSG was associated with dental caries and gingivitis in the study population. The overall salivary bacterial load in saliva decreased with increasing salivary glucose concentration. Under HSG conditions, the bacterial count for 35 (83% of 42 species was significantly reduced, and relative bacterial frequencies in 27 species (64% were altered, as compared with LSG conditions. These alterations were stronger predictors of high salivary glucose than measures of oral disease, obesity, sleep or fitness.HSG was associated with a reduction in overall bacterial load and alterations to many relative bacterial frequencies in saliva when compared with LSG in samples from adolescents. We propose that hyperglycemia due to obesity and/or T2D results in HSG and subsequent acidification of the oral environment, leading to a generalized perturbation in the oral microbiome. This suggests a basis for the observation that hyperglycemia is associated with an increased risk of dental erosion, dental caries, and gingivitis. We conclude that HSG in adolescents may be predicted from salivary microbial diversity or frequency, and that the changes in the oral microbial composition seen in adolescents with developing metabolic disease may the consequence of hyperglycemia.

  3. 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

  4. Fermentation of mixed glucose-xylose substrates by engineered strains of Saccharomyces cerevisiae: role of the coenzyme specificity of xylose reductase, and effect of glucose on xylose utilization

    Directory of Open Access Journals (Sweden)

    Klimacek Mario

    2010-03-01

    Full Text Available Abstract Background In spite of the substantial metabolic engineering effort previously devoted to the development of Saccharomyces cerevisiae strains capable of fermenting both the hexose and pentose sugars present in lignocellulose hydrolysates, the productivity of reported strains for conversion of the naturally most abundant pentose, xylose, is still a major issue of process efficiency. Protein engineering for targeted alteration of the nicotinamide cofactor specificity of enzymes catalyzing the first steps in the metabolic pathway for xylose was a successful approach of reducing xylitol by-product formation and improving ethanol yield from xylose. The previously reported yeast strain BP10001, which expresses heterologous xylose reductase from Candida tenuis in mutated (NADH-preferring form, stands for a series of other yeast strains designed with similar rational. Using 20 g/L xylose as sole source of carbon, BP10001 displayed a low specific uptake rate qxylose (g xylose/g dry cell weight/h of 0.08. The study presented herein was performed with the aim of analysing (external factors that limit qxylose of BP10001 under xylose-only and mixed glucose-xylose substrate conditions. We also carried out a comprehensive investigation on the currently unclear role of coenzyme utilization, NADPH compared to NADH, for xylose reduction during co-fermentation of glucose and xylose. Results BP10001 and BP000, expressing C. tenuis xylose reductase in NADPH-preferring wild-type form, were used. Glucose and xylose (each at 10 g/L were converted sequentially, the corresponding qsubstrate values being similar for each strain (glucose: 3.0; xylose: 0.05. The distribution of fermentation products from glucose was identical for both strains whereas when using xylose, BP10001 showed enhanced ethanol yield (BP10001 0.30 g/g; BP000 0.23 g/g and decreased yields of xylitol (BP10001 0.26 g/g; BP000 0.36 g/g and glycerol (BP10001 0.023 g/g; BP000 0.072 g/g as compared

  5. Utilizing hyaluronic acid as a versatile platform for fluorescence resonance energy transfer-based glucose sensing.

    Science.gov (United States)

    Ge, Minghao; Bai, Pengli; Chen, Mingli; Tian, Jingjing; Hu, Jun; Zhi, Xu; Yin, Huancai; Yin, Jian

    2018-03-01

    Here, we utilized the ultrasonic emulsification technique to generate hyaluronic acid microspheres incorporating a fluorescence-based glucose biosensor. We synthesized a novel lanthanide ion luminophore based on Eu 3+ . Eu sulfosuccinimidyl dextran (Eu-dextran) and Alexa Fluor 647 sulfosuccinimidyl-ConA (Alexa Fluor 647-ConA) were encapsulated in hyaluronic acid hydrogel to generate microspheres. Glucose sensing was carried out using a fluorescence resonance energy transfer (FRET)-based assay principle. A proportional fluorescence intensity increase was found within a 0.5-10-mM glucose concentration range. The glucose-sensing strategy showed an excellent tolerance for potential interferents. Meanwhile, the fluorescent signal of hyaluronic acid microspheres was very stable after testing for 72 h in glucose solution. Overall, hyaluronic acid microspheres encapsulating sensing biomolecules offer a stable and biocompatible biosensor for a variety of applications including cell culture systems, tissue engineering, detection of blood glucose, etc. Graphical abstract We report an ingenious biosensor encapsulated in hyaluronic acid microspheres for monitoring of glucose. Glucose sensing is carried out using a fluorescence resonance energy transfer-based assay principle with a novel lanthanide ions luminophore. The glucose detection system has excellent biocompatibility and stability for monitoring of glucose.

  6. Agricultural management legacy affects microbial energetics, resource utilization and active bacterial community membership during 13C-glucose consumption

    Science.gov (United States)

    Helgason, B. L.; Levy-Booth, D.; Arcand, M. M.

    2017-12-01

    Over the long-term, differences in soil management can result in fundamental changes in biogeochemical cycling. The Alternative Cropping Systems (ACS) Study at Scott, SK, Canada (est. 1994) compares organic (ORG) vs. conventionally (CON) managed crop rotations in a loamy Typic Borall. Nitrogen (N) and phosphorus (P) deficiency in the ORG systems have limited crop growth and thus plant carbon (C) inputs for over two decades, ultimately resulting in a C deficiency which has further altered biogeochemical cycling. We conducted a short-term microcosm experiment using 13C-glucose stable isotope probing (SIP) of DNA to test whether ORG soils have greater microbial C use efficiency due to long term resource limitation. Glucose-utilizing populations were dominated by Proteobacteria and Actinobacteria, with differing species-level identities and physiological capacities between CON and ORG systems. Of the 13C-utilizing taxa, relative abundance of Proteobacteria was greater in CON while Actinobacteria (and notably Firmicutes) were more dominant in ORG soils. Using isothermal calorimetry, we measured a thermodynamic efficiency (ηeff) of 0.68, which was not significantly different between soils indicating that the metabolic cost of glucose utilization was similar in CON and ORG soils. In spite of this, differential abundance analysis of 13C-labelled OTUs revealed that ORG soils had distinct active bacterial populations that were positively correlated with ηeff, ηsoil (glucose energy retained in soil) and primed soil organic matter (pSOM). In contrast, differentially abundant OTUs in the CON soils were negatively correlated with measures of thermodynamic efficiency but positively correlated with glucose-derived heat and CO2 production as well as NO3- and PO4- availability. ORG bacterial communities may co-metabolize other resources (N and P) from SOM to meet their metabolic requirements during glucose utilization, while the active bacteria in the CON soils could access these

  7. Age-dependent alterations of glucose clearance and homeostasis are temporally separated and modulated by dietary fat

    DEFF Research Database (Denmark)

    Damgaard, Mads Thue Fejerskov; Pærregaard, Simone I.; Søgaard, Ida

    2018-01-01

    -sucrose diets based on either fish oil (FOD) or soybean oil (SOD), rich in ω3- and ω6-polyunsaturated fatty acids, respectively, to closely monitor the age-dependent development in glucose regulation in both obese (SOD-fed) and lean (LFD- and FOD-fed) mice. We assessed glucose homeostasis and glucose clearance...... at week 8, 12, 16, 24, 31, and 39 and performed an insulin tolerance test at week 40. We further analyzed correlations between the gut microbiota and key metabolic parameters. Interestingly, alterations in glucose homeostasis and glucose clearance were temporally separated, while 16S ribosomal gene...... amplicon sequencing revealed that gut microbial alterations formed correlation clusters with fat mass and either glucose homeostasis or glucose clearance, but rarely both. Importantly, effective glucose clearance was maintained in FOD- and even increased in LFD-fed mice, whereas SOD-fed mice rapidly...

  8. 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

  9. Diabetes Alters the Expression and Translocation of the Insulin-Sensitive Glucose Transporters 4 and 8 in the Atria

    Science.gov (United States)

    Maria, Zahra; Campolo, Allison R.; Lacombe, Veronique A.

    2015-01-01

    Although diabetes has been identified as a major risk factor for atrial fibrillation, little is known about glucose metabolism in the healthy and diabetic atria. Glucose transport into the cell, the rate-limiting step of glucose utilization, is regulated by the Glucose Transporters (GLUTs). Although GLUT4 is the major isoform in the heart, GLUT8 has recently emerged as a novel cardiac isoform. We hypothesized that GLUT-4 and -8 translocation to the atrial cell surface will be regulated by insulin and impaired during insulin-dependent diabetes. GLUT protein content was measured by Western blotting in healthy cardiac myocytes and type 1 (streptozotocin-induced, T1Dx) diabetic rodents. Active cell surface GLUT content was measured using a biotinylated photolabeled assay in the perfused heart. In the healthy atria, insulin stimulation increased both GLUT-4 and -8 translocation to the cell surface (by 100% and 240%, respectively, Pinsulin stimulation, we reported an increase in Akt (Th308 and s473 sites) and AS160 phosphorylation, which was positively (Pinsulin signaling pathway. This was confirmed by the rescued translocation of GLUT-4 and -8 to the atrial cell surface upon insulin stimulation in the atria of type 1 diabetic subjects. In conclusion, our data suggest that: 1) both GLUT-4 and -8 are insulin-sensitive in the healthy atria through an Akt/AS160 dependent pathway; 2) GLUT-4 and -8 trafficking is impaired in the diabetic atria and rescued by insulin treatment. Alterations in atrial glucose transport may induce perturbations in energy production, which may provide a metabolic substrate for atrial fibrillation during diabetes. PMID:26720696

  10. Opium can differently alter blood glucose, sodium and potassium in male and female rats.

    Science.gov (United States)

    Karam, Gholamreza Asadi; Rashidinejad, Hamid Reza; Aghaee, Mohammad Mehdi; Ahmadi, Jafar; Rahmani, Mohammad Reza; Mahmoodi, Mehdi; Azin, Hosein; Mirzaee, Mohammad Reza; Khaksari, Mohammad

    2008-04-01

    To determine the effects of opium on serum glucose, potassium and sodium in male and female Wistar rat, opium solution (60 mg/kg) injected intraperitoneally and the same volume of distilled water was used as control (7 rats in each group). Blood samples were collected at 0, 30, 60, 120, 240 and 360 minutes after injection from orbit cavity and the values of serum glucose, sodium (Na(+)) and potassium (K(+)) were measured. The data were then analyzed by the repeated measure ANOVA based on sex and case-control group. P opium solution injection, in female rats compared to a control group. However, the male rats had this rise at 30, 60 and 120 minutes after opium solution injection compared to control group. While serum glucose in male rats was significantly higher than females at 30, 60 and 120 minutes, this value was higher in the female rats at 360 minutes. Therefore, serum glucose alterations following opium injection was significantly different in groups and in the sexes at different times. Sodium (Na(+)) rose at 60, 240 and 360 minutes significantly in all rats compared to control group. However, sodium alteration following opium injection was significantly different only between treated and control groups but sex-independent at all times. Potassium (K(+)) increased significantly at 60, 120, 240 and 360 minutes in male rats, compared to a control group. In female rats K(+) significantly raised at 30, 120, 240 and 360 minutes. Therefore, the alteration of K(+) in male and female rats was found time dependent and sex independent. According to our results, opium increased serum glucose in male and female rats differently, and it interferes with metabolic pathways differently on a gender dependent basis. Opium raised serum Na(+) and K(+), thus it interfere with water regulation and blood pressure via different mechanism.

  11. Effects of pregnancy and fasting on muscle glucose utilization in the rabbit.

    Science.gov (United States)

    Hauguel, S; Leturque, A; Gilbert, M; Girard, J

    1988-05-01

    The effects of fasting on maternal glucose metabolism were investigated in nonpregnant and 29-day pregnant conscious rabbits. Pregnancy decreased the glucose metabolic index by 60% in maternal red postural muscles. Fasting induced similar modifications in nonpregnant rabbits and exaggerated the changes observed in fed pregnant animals. These data suggest that the decreased glucose utilization by maternal red muscles observed during pregnancy and fasting is related to the increase in circulating fat-derived substrates, because the fall in plasma insulin concentration is a specific adaptation to fasting.

  12. Alteration of postprandial glucose and insulin concentrations with meal frequency and composition.

    Science.gov (United States)

    Kanaley, Jill A; Heden, Timothy D; Liu, Ying; Fairchild, Timothy J

    2014-11-14

    A frequent eating pattern may alter glycaemic control and augment postprandial insulin concentrations in some individuals due to the truncation of the previous postprandial period by a subsequent meal. The present study examined glucose, insulin, C-peptide and glucose-dependent insulinotropic peptide (GIP) responses in obese individuals when meals were ingested in a high-frequency pattern (every 2 h, 6M) or in a low-frequency pattern (every 4 h, 3M) over 12 h. It also examined these postprandial responses to high-frequency, high-protein meals (6MHP). In total, thirteen obese subjects completed three 12 h study days during which they consumed 6276 kJ (1500 kcal): (1) 3M - 15 % protein and 65 % carbohydrate; (2) 6M - 15 % protein and 65 % carbohydrate; (3) 6MHP - 45 % protein and 35 % carbohydrate. Blood samples were collected every 10 min and analysed for glucose, insulin, C-peptide and GIP. Insulin total AUC (tAUC) and peak insulin concentrations (Pmeal frequency or composition. In obese subjects, ingestion of meals in a low-frequency pattern does not alter glucose tAUC, but increases postprandial insulin responses. The substitution of carbohydrates with protein in a frequent meal pattern results in tighter glycaemic control and reduced postprandial insulin responses.

  13. Altered Skeletal Muscle Fatty Acid Handling in Subjects with Impaired Glucose Tolerance as Compared to Impaired Fasting Glucose

    Directory of Open Access Journals (Sweden)

    Gijs H. Goossens

    2016-03-01

    Full Text Available Altered skeletal muscle fatty acid (FA metabolism contributes to insulin resistance. Here, we compared skeletal muscle FA handling between subjects with impaired fasting glucose (IFG; n = 12 (7 males and impaired glucose tolerance (IGT; n = 14 (7 males by measuring arterio-venous concentration differences across forearm muscle. [2H2]-palmitate was infused intravenously, labeling circulating endogenous triacylglycerol (TAG and free fatty acids (FFA, whereas [U-13C]-palmitate was incorporated in a high-fat mixed-meal, labeling chylomicron-TAG. Skeletal muscle biopsies were taken to determine muscle TAG, diacylglycerol (DAG, FFA, and phospholipid content, their fractional synthetic rate (FSR and degree of saturation, and gene expression. Insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp. Net skeletal muscle glucose uptake was lower (p = 0.018 and peripheral insulin sensitivity tended to be reduced (p = 0.064 in IGT as compared to IFG subjects. Furthermore, IGT showed higher skeletal muscle extraction of VLDL-TAG (p = 0.043, higher muscle TAG content (p = 0.025, higher saturation of FFA (p = 0.004, lower saturation of TAG (p = 0.017 and a tendency towards a lower TAG FSR (p = 0.073 and a lower saturation of DAG (p = 0.059 versus IFG individuals. Muscle oxidative gene expression was lower in IGT subjects. In conclusion, increased liver-derived TAG extraction and reduced lipid turnover of saturated FA, rather than DAG content, in skeletal muscle accompany the more pronounced insulin resistance in IGT versus IFG subjects.

  14. Effect of hyperbaric oxygen on glucose utilization in a freeze-traumatized rat brain

    International Nuclear Information System (INIS)

    Contreras, F.L.; Kadekaro, M.; Eisenberg, H.M.

    1988-01-01

    Local cerebral glucose utilization was measured with the autoradiographic 2-deoxyglucose technique in rats injured by a focal parietal cortical freeze lesion then treated with hyperbaric oxygen (HBO). The cold lesion depressed glucose utilization in the contralateral as well as in the ipsilateral hemisphere. The largest decreases were observed in ipsilateral cortical areas. Treatment of lesioned animals with HBO at 2 atm for 90 minutes on each of 4 consecutive days tended to increase the overall cerebral glucose utilization measured 5 days after injury when compared to animals exposed to normobaric air. This improvement reached statistical significance in five of the 21 structures studied: the auditory cortex, medial geniculate body, superior olivary nucleus, and lateral geniculate body ipsilateral to the lesion, and the mammillary body. The data indicate that changes in lesioned rats exposed to HBO are not restricted to the period of time that the animals are in the hyperbaric chamber but are persistent

  15. Alteration of hypothalamic glucose and lactate sensing in 48h hyperglycemic rats.

    Science.gov (United States)

    Allard, Camille; Carneiro, Lionel; Collins, Stephan C; Chrétien, Chloé; Grall, Sylvie; Pénicaud, Luc; Leloup, Corinne

    2013-02-08

    Hypothalamic detection of nutrients is involved in the control of energy metabolism and is altered in metabolic disorders. Although hypothalamic detection of blood lactate lowers hepatic glucose production and food intake, it is unknown whether it also modulates insulin secretion. To address this, a lactate injection via the right carotid artery (cephalad) was performed in Wistar rats. This triggered a transient increase in insulin secretion. Rats made hyperglycemic for 48h exhibited prolonged insulin secretion in response to a glucose injection via the carotid artery, but lactate injection induced two types of responses: half of the HG rats showed no difference compared to controls and the other half had markedly decreased insulin secretion. Astroglial monocarboxylates transporters MCT1 and MCT4 isoforms transfer lactate from blood to astrocytes and release lactate to the extracellular space, whilst the neuronal MCT2 isoform permits neuronal lactate uptake. We found that astroglial MCT1 and MCT4, and neuronal MCT2 protein levels in the medio-basal hypothalamus (MBH) were not modified by 48h-hyperglycemia. Together, these results indicate that hypothalamic sensing of circulating lactate triggers insulin secretion. Both glucose and lactate sensing are altered in a model of hyperglycemia, without alteration of MBH MCTs protein levels. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. Effect of lonidamine on the utilization of 14C-labeled glucose by human astrocytoma cells

    International Nuclear Information System (INIS)

    Paggi, M.G.; Zupi, G.; Fanciulli, M.; Del Carlo, C.; Giorno, S.; Laudonio, N.; Silvestrini, B.; Caputo, A.; Floridi, A.

    1987-01-01

    The effect of lonidamine (LND), 1-(2,4-dichlorobenzyl)-1H-indazol-3 carboxylic acid, on the utilization of carbon from 14 C-labeled glucose by cell cultures of the permanent strain LI derived from a human glioblastoma multiforme (astrocytoma) has been investigated. The results may be summarized as follows. Aerobic glycolysis is the main energy-yielding process as shown by the fact that the greatest part of glucose carbon atoms is incorporated into lactate. Nevertheless, the amount of glucose converted accounts for only 63% of the lactate produced, indicating the presence of an elevated endogenous aerobic glycolysis. The amount of glucose carbon atoms incorporated into CO 2 , lipids, nucleic acid, and supporting structures is low. LND decreased the incorporation of 14 C activity in all the above mentioned isolated compounds because of its ability to inhibit glucose phosphorylation. Consequently, there is a lower concentration of glucose-6-phosphate which, in turn, affects the rate of formation of several metabolites in glycolytic and pentose phosphate pathways. Experiments with [1- 14 C]-2-deoxy-D-glucose further substantiate the idea of glucose phosphorylation as a main target of LND and strongly suggest the presence of a mitochondrially bound hexokinase. The higher inhibition of glucose phosphorylation in exponentially growing cells indicates a further shift of the enzyme toward mitochondria-bound form and confirms the importance of the energy status of the cell in eliciting the response to LND. The reduced capacity of LND-treated cells to synthetize ATP and glucose-6-phosphate reflects the decreased synthesis of proteins and nucleic acids, which affects cell growth and duplication

  17. Production of Acetoin through Simultaneous Utilization of Glucose, Xylose, and Arabinose by Engineered Bacillus subtilis.

    Directory of Open Access Journals (Sweden)

    Bo Zhang

    Full Text Available Glucose, xylose and arabinose are the three most abundant monosaccharide found in lignocellulosic biomass. Effectively and simultaneously utilization of these sugars by microorganisms for production of the biofuels and bio-chemicals is essential toward directly fermentation of the lignocellulosic biomass. In our previous study, the recombinant Bacillus subtilis 168ARSRCPΔacoAΔbdhA strain was already shown to efficiently utilize xylose for production of acetoin, with a yield of 0.36 g/g xylose. In the current study, the Bacillus subtilis168ARSRCPΔacoAΔbdhA strain was further engineered to produce acetoin from a glucose, xylose, and arabinose mixtures. To accomplish this, the endogenous xylose transport protein AraE, the exogenous xylose isomerase gene xylA and the xylulokinase gene xylB from E. coli were co-overexpressed in the Bacillus subtilis 168ARSRCPΔacoAΔbdhA strain, which enabled the resulting strain, denoted ZB02, to simultaneously utilize glucose and xylose. Unexpectedly, the ZB02 strain could simultaneously utilize glucose and arabinose also. Further results indicated that the transcriptional inhibition of the arabinose transport protein gene araE was the main limiting factor for arabinose utilization in the presence of glucose. Additionally, the arabinose operon in B. subtilis could be activated by the addition of arabinose, even in the presence of glucose. Through fed-batch fermentation, strain ZB02 could simultaneously utilize glucose, xylose, and arabinose, with an average sugar consumption rate of 3.00 g/l/h and an average production of 62.2 g/l acetoin at a rate of 0.864 g/l/h. Finally, the strain produced 11.2 g/l acetoin from lignocellulosic hydrolysate (containing 20.6g/l glucose, 12.1 g/l xylose and 0.45 g/l arabinose in flask cultivation, with an acetoin yield of 0.34 g/g total sugar. The result demonstrates that this strain has good potential for the utilization of lignocellulosic hydrolysate for production of acetoin.

  18. A simple method for measuring glucose utilization of insulin-sensitive tissues by using the brain as a reference

    International Nuclear Information System (INIS)

    Namba, Hiroki; Nakagawa, Keiichi; Iyo, Masaomi; Fukushi, Kiyoshi; Irie, Toshiaki

    1994-01-01

    A simple method, without measurement of the plasma input function, to obtain semiquantitative values of glucose utilization in tissues other than the brain with radioactive deoxyglucose is reported. The brain, in which glucose utilization is essentially insensitive to plasma glucose and insulin concentrations, was used as an internal reference. The effects of graded doses of oral glucose loading (0.5, 1 and 2 mg/g body weight) on insulin-sensitive tissues (heart, muscle and fat tissue) were studied in the rat. By using the brain-reference method, dose-dependent increases in glucose utilization were clearly shown in all the insulin-sensitive tissues examined. The method seems to be of value for measurement of glucose utilization using radioactive deoxyglucose and positron emission tomography in the heart or other insulin-sensitive tissues, especially during glucose loading. (orig.)

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

    Science.gov (United States)

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

    2016-04-01

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

  20. Simultaneous utilization of glucose and xylose for lipid production by Trichosporon cutaneum

    Directory of Open Access Journals (Sweden)

    Jin Guojie

    2011-08-01

    Full Text Available Abstract Background Biochemical conversion of lignocellulose hydrolysates remains challenging, largely because most microbial processes have markedly reduced efficiency in the presence of both hexoses and pentoses. Thus, identification of microorganisms capable of efficient and simultaneous utilization of both glucose and xylose is pivotal to improving this process. Results In this study, we found that the oleaginous yeast strain Trichosporon cutaneum AS 2.571 assimilated glucose and xylose simultaneously, and accumulated intracellular lipid up to 59 wt% with a lipid coefficient up to 0.17 g/g sugar, upon cultivation on a 2:1 glucose/xylose mixture in a 3-liter stirred-tank bioreactor. In addition, no classic pattern of diauxic growth behavior was seen; the microbial cell mass increased during the whole culture process without any lag periods. In shake-flask cultures 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. Simultaneous utilization of glucose and xylose was also seen during fermentation of corn-stover hydrolysate with a lipid content and coefficient of 39.2% and 0.15 g/g sugar, respectively. The lipid produced had a fatty-acid compositional profile similar to those of conventional vegetable oil, indicating that it could have potential as a raw material for biodiesel production. Conclusion Efficient lipid production with simultaneous consumption of glucose and xylose was achieved in this study. This process provides an exciting opportunity to transform lignocellulosic materials into biofuel molecules, and should also encourage further study to elucidate this unique sugar-assimilation mechanism.

  1. Effect of gender on glucose utilization rates in healthy humans: A positron emission tomography study

    International Nuclear Information System (INIS)

    Miura, S.A.; Schapiro, M.B.; Grady, C.L.; Kumar, A.; Salerno, J.A.; Kozachuk, W.E.; Wagner, E.; Rapoport, S.I.; Horwitz, B.

    1990-01-01

    Positron emission tomography (PET) was used with 18fluorodeoxyglucose to see if gender differences in resting cerebral glucose utilization could be detected. Thirty-two healthy subjects (15 women and 17 men; age range: 21-38 yr) were examined using a high-resolution PET scanner to determine the regional cerebral metabolic rate for glucose (CMRglc) in 65 gray matter regions of interest. Whole brain CMRglc did not differ significantly between the two genders, nor did any of the regional CMRglc values. Only 1 of 65 ratios of regional-to-whole brain CMRglc differed significantly between men and women, which is consistent with chance. These results indicate that there are no differences in resting regional cerebral glucose utilization between young men and women

  2. Co-Utilization of Glucose and Xylose for Enhanced Lignocellulosic Ethanol Production with Reverse Membrane Bioreactors

    Directory of Open Access Journals (Sweden)

    Mofoluwake M. Ishola

    2015-12-01

    Full Text Available Integrated permeate channel (IPC flat sheet membranes were examined for use as a reverse membrane bioreactor (rMBR for lignocellulosic ethanol production. The fermenting organism, Saccharomyces cerevisiae (T0936, a genetically-modified strain with the ability to ferment xylose, was used inside the rMBR. The rMBR was evaluated for simultaneous glucose and xylose utilization as well as in situ detoxification of furfural and hydroxylmethyl furfural (HMF. The synthetic medium was investigated, after which the pretreated wheat straw was used as a xylose-rich lignocellulosic substrate. The IPC membrane panels were successfully used as the rMBR during the batch fermentations, which lasted for up to eight days without fouling. With the rMBR, complete glucose and xylose utilization, resulting in 86% of the theoretical ethanol yield, was observed with the synthetic medium. Its application with the pretreated wheat straw resulted in complete glucose consumption and 87% xylose utilization; a final ethanol concentration of 30.3 g/L was obtained, which corresponds to 83% of the theoretical yield. Moreover, complete in situ detoxification of furfural and HMF was obtained within 36 h and 60 h, respectively, with the rMBR. The use of the rMBR is a promising technology for large-scale lignocellulosic ethanol production, since it facilitates the co-utilization of glucose and xylose; moreover, the technology would also allow the reuse of the yeast for several batches.

  3. Insulin and Glucose Alter Death-Associated Protein Kinase 3 (DAPK3) DNA Methylation in Human Skeletal Muscle

    DEFF Research Database (Denmark)

    Mudry, Jonathan M; Lassiter, David G; Nylén, Carolina

    2017-01-01

    of selected genes was determined in muscle from healthy and type 2 diabetic men before and after a glucose tolerance test. Insulin altered DNA methylation in the 3'UTR of the calcium pump ATP2A3 gene. Insulin increased DNA methylation in the gene body of DAPK3, a gene involved in cell proliferation, apoptosis......DNA methylation is altered by environmental factors. We hypothesized DNA methylation is altered in skeletal muscle in response to either insulin or glucose exposure. We performed a genome-wide DNA methylation analysis in muscle from healthy men before and after insulin exposure. DNA methylation...... glucose incorporation to glycogen was unaltered by siRNA against DAPK3, palmitate oxidation was increased. In conclusion, insulin and glucose exposure acutely alter the DNA methylation profile of skeletal muscle, indicating DNA methylation constitutes a rapidly and adaptive epigenetic mark. Furthermore...

  4. Adenovirus infection results in alterations of insulin signaling and glucose homeostasis

    Science.gov (United States)

    Jiang, Shaoning; Gavrikova, Tatyana A.; Pereboev, Alexander

    2010-01-01

    Recombinant adenovirus (Ad) vectors can initiate an inflammatory response, limiting its use in gene therapy and basic research. Despite increased efforts to better understand Ad infection, little is known about how it affects cellular metabolic responses. In the current studies, we explored the effects of Ad vectors on insulin signaling molecules and glucose homeostasis. Nonreplicative Ad vectors were injected into rats through the tail vein, and at 4–13 days postinjection insulin signaling and glucose tolerance were examined. Ad vector infection significantly reduced total levels of the insulin receptor (IR), and insulin receptor substrates 1 and 2 (IRS-1, IRS-2) in the liver of rats, resulting in decreased insulin-induced tyrosine phosphorylation of IR, IRS-1, and IRS-2, and decreased interaction of IRS-1 and IRS-2 with phosphoinositide 3-kinase (PI3K). In addition, Ad infection resulted in impaired systemic glucose homeostasis, which recovered by 13 days, after the protein levels of IR, IRS-1, and IRS-2 had started to normalize. Expression of a TNF inhibitor or Kupffer cell depletion attenuated the Ad vector-induced decreases of insulin signaling molecules, indicating a potential role of Kupffer cell activation in this process. These studies provide evidence that systemic administration of Ad vectors can impair insulin signaling in liver, resulting in altered systemic glucose metabolism. Thus, effects of Ad vector infection on insulin action and glucose metabolism need to be considered when Ad vectors are used in research or gene therapy and may be more broadly applicable to other viral agents. PMID:20388825

  5. miR-182 Regulates Metabolic Homeostasis by Modulating Glucose Utilization in Muscle

    Directory of Open Access Journals (Sweden)

    Duo Zhang

    2016-07-01

    Full Text Available Understanding the fiber-type specification and metabolic switch in skeletal muscle provides insights into energy metabolism in physiology and diseases. Here, we show that miR-182 is highly expressed in fast-twitch muscle and negatively correlates with blood glucose level. miR-182 knockout mice display muscle loss, fast-to-slow fiber-type switching, and impaired glucose metabolism. Mechanistic studies reveal that miR-182 modulates glucose utilization in muscle by targeting FoxO1 and PDK4, which control fuel selection via the pyruvate dehydrogenase complex (PDHC. Short-term high-fat diet (HFD feeding reduces muscle miR-182 levels by tumor necrosis factor α (TNFα, which contributes to the upregulation of FoxO1/PDK4. Restoration of miR-182 expression in HFD-fed mice induces a faster muscle phenotype, decreases muscle FoxO1/PDK4 levels, and improves glucose metabolism. Together, our work establishes miR-182 as a critical regulator that confers robust and precise controls on fuel usage and glucose homeostasis. Our study suggests that a metabolic shift toward a faster and more glycolytic phenotype is beneficial for glucose control.

  6. Use of anesthesia dramatically alters the oral glucose tolerance and insulin secretion in C57Bl/6 mice

    DEFF Research Database (Denmark)

    Windeløv, Johanne A; Pedersen, Jens; Holst, Jens J

    2016-01-01

    Evaluation of the impact of anesthesia on oral glucose tolerance in mice. Anesthesia is often used when performing OGTT in mice to avoid the stress of gavage and blood sampling, although anesthesia may influence gastrointestinal motility, blood glucose, and plasma insulin dynamics. C57Bl/6 mice...... in the time frame -15 to +150 min. Plasma insulin concentration was measured at time 0 and 20 min. All four anesthetic regimens resulted in impaired glucose tolerance compared to saline/no anesthesia. (1) hypnorm/midazolam increased insulin concentrations and caused an altered glucose tolerance; (2) ketamine...... regimens altered the oral glucose tolerance, and we conclude that anesthesia should not be used when performing metabolic studies in mice....

  7. Alterations in glucose and protein metabolism in animals subjected to simulated microgravity

    Science.gov (United States)

    Mondon, C. E.; Rodnick, K. J.; Azhar, S.; Reaven, G. M.; Dolkas, C. B.

    1992-01-01

    Reduction of physical activity due to disease or environmental restraints, such as total bed rest or exposure to spaceflight, leads to atrophy of skeletal muscle and is frequently accompanied by alterations in food intake and the concentration of metabolic regulatory hormones such as insulin. Hindlimb suspension of laboratory rats, as a model for microgravity, also shows marked atrophy of gravity-dependent muscles along with a reduced gain in body weight. Suspended rats exhibit enhanced sensitivity to insulin-induced glucose uptake when compared with normal control rats and resistance to insulin action when compared with control rats matched similarly for reduced body weight gain. These changes are accompanied by decreased insulin binding and tyrosine kinase activity in soleus but not plantaris muscle, unchanged glucose uptake by perfused hindlimb and decreased sensitivity but not responsiveness to insulin-induced suppression of net proteolysis in hindlimb skeletal muscle. These findings suggest that loss of insulin sensitivity during muscle atrophy is associated with decreased insulin binding and tyrosine kinase activity in atrophied soleus muscle along with decreased sensitivity to the effects of insulin on suppressing net protein breakdown but not on enhancing glucose uptake by perfused hindlimb.

  8. Association between the pattern of IGFBP-1 alteration and the glucose/insulin metabolic control.

    Science.gov (United States)

    Nedić, O; Masnikosa, R; Lagundžin, D

    2011-05-01

    Little is known on the possible association between impaired glucose/insulin metabolism, the pattern of IGFBP-1 phosphorylation and the complex formation with other serum proteins. In this study, the concentration, isoform, multimer and complex pattern of IGFBP-1 was compared in healthy persons and patients with type 2 diabetes mellitus or with hypoglycemia. Concentrations of insulin and IGFBP-1 were determined by radioimmunoassay. Metal affinity and immunoaffinity chromatography were used for the separation of molecular forms of IGFBP-1, which were detected by immunoblotting and SELDI. The counter directional change in insulin and IGFBP-1 concentrations, expressed as a factor that takes into consideration the rate of insulin increase and IGFBP-1 decrease after glucose intake was approximately twice more pronounced in patients with diabetes than in healthy and hypoglycemic persons. The alteration in the phosphorylation pattern of IGFBP-1 due to diabetes or hypoglycemia was not observed. IGFBP-1 multimers found in the circulation of patients with diabetes type 2 differed from those detected in the circulation of others: there were 3 molecular forms between 90 and 100 kDa (compared to one in patients with hypoglycemia or 2 in healthy persons), 2 of which were α (2)M-reactive and one not. These results suggest a possible greater involvement of IGF system in glucose regulation in patients with diabetes type 2. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

  9. Alterations in glucose and protein metabolism in animals subjected to simulated microgravity

    Science.gov (United States)

    Mondon, C. E.; Rodnick, K. J.; Dolkas, C. B.; Azhar, S.; Reaven, G. M.

    1992-09-01

    Reduction of physical activity due to disease or environmental restraints, such as total bed rest or exposure to spaceflight, leads to atrophy of skeletal muscle and is frequently accompanied by alterations in food intake and the concentration of metabolic regulatory hormones such as insulin. Hindlimb suspension of laboratory rats, as a model for microgravity, also shows marked atrophy of gravity dependent muscles along with a reduced gain in body weight. Suspended rats exhibit enhanced sensitivity to insulin-induced glucose uptake when compared with normal control rats and resistance to insulin action when compared with control rats matched similarly for reduced body weight gain. These changes are accompanied by decreased insulin binding and tyrosine kinase activity in soleus but not plantaris muscle, unchanged glucose uptake by perfused hindlimb and decreased sensitivity but not responsiveness to insulin-induced suppression of net proteolysis in hindlimb skeletal muscle. These findings suggest that loss of insulin sensitivity during muscle atrophy is associated with decreased insulin binding and tyrosine kinase activity in atrophied soleus muscle along with decreased sensitivity to the effects of insulin on suppressing net protein breakdown but not on enhancing glucose uptake by perfused hindlimb.

  10. Exposure to 2,4-dichlorophenoxyacetic acid alters glucose metabolism in immature rat Sertoli cells.

    Science.gov (United States)

    Alves, M G; Neuhaus-Oliveira, A; Moreira, P I; Socorro, S; Oliveira, P F

    2013-07-01

    The purpose of this study was to determine the effects of 2,4-D, an herbicide used worldwide also known as endocrine disruptor, in Sertoli cell (SC) metabolism. Immature rat SCs were maintained 50h under basal conditions or exposed to 2,4-D (100nM, 10μM and 1mM). SCs exposed to 10μM and 1mM of 2,4-D presented lower intracellular glucose and lactate content. Exposure to 10μM of 2,4-D induced a significant decrease in glucose transporter-3 mRNA levels and phosphofructokinase-1 mRNA levels decreased in cells exposed to 100nM and 10μM of 2,4-D. Exposure to 100nM and 10μM also induced a decrease in lactate dehydrogenase (LDH) mRNA levels while the LDH protein levels were only decreased in cells exposed to 1mM of 2,4-D. Exposure to 2,4-D altered glucose uptake and metabolization in SCs, as well as lactate metabolism and export that may result in impaired spermatogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. 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

  12. 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.

  13. Immune Alterations in Male and Female Mice after 2-Deoxy-D-Glucose Administration

    Science.gov (United States)

    Dreau, Didier; Morton, Darla S.; Foster, Mareva; Swiggett, Jeanene P.; Sonnenfeld, Gerald

    1995-01-01

    Administration of 2-deoxy-D-glucose (2-DG), an analog of glucose which inhibits glycolysis by competitive antagonism for phosphohexose isomerase, results in acute periods of intracellular glucoprivation and hyperglycemia resulting in hyperphagia. In addition to these changes in the carbohydrate metabolism, injection of 2-DG results in alterations of both the endocrine and neurological systems as suggested by modifications in oxytocin and glucocorticoid levels and norepinephrine production. Moreover, alterations of the immune response, such as a decrease in the in vitro proliferation of splenocytes after mitogen-stimulation, were observed in mice injected with 2-DG. Sex, genotype and environment are among the factors that may modulate effects of catecholamines and hypothalamo-pituitary-adrenal axis on these immune changes. Sexual dimorphism in immune function resulting from the effects of sex hormones on immune effector cells has been shown in both animals and humans. These observations have important implications, especially with regard to higher incidence of many autoimmune diseases in females. Evidence exists that reproductive hormones influence the immune system and increase the risk of immunologically related disorders in both animals and humans. Indeed, immunological responses in stressful situations may also be confounded by fluctuations of sex hormones especially in females. Lymphocyte distribution, cytoldne production, and the ability of lymphocyte to proliferate in vitro were analyzed in male and female mice to determine if sex influenced 2-DG immunomodulation. In addition, the influence of hormones, especially sex hormones, on these changes were evaluated.

  14. Engineering E. coli for simultaneous glucose-xylose utilization during methyl ketone production.

    Science.gov (United States)

    Wang, Xi; Goh, Ee-Been; Beller, Harry R

    2018-01-27

    We previously developed an E. coli strain that overproduces medium-chain methyl ketones for potential use as diesel fuel blending agents or as flavors and fragrances. To date, the strain's performance has been optimized during growth with glucose. However, lignocellulosic biomass hydrolysates also contain a substantial portion of hemicellulose-derived xylose, which is typically the second most abundant sugar after glucose. Commercialization of the methyl ketone-producing technology would benefit from the increased efficiency resulting from simultaneous, rather than the native sequential (diauxic), utilization of glucose and xylose. In this study, genetic manipulations were performed to alleviate carbon catabolite repression in our most efficient methyl ketone-producing strain. A strain engineered for constitutive expression of xylF and xylA (involved in xylose transport and metabolism) showed synchronized glucose and xylose consumption rates. However, this newly acquired capability came at the expense of methyl ketone titer, which decreased fivefold. Further efforts were made to improve methyl ketone production in this strain, and we found that two strategies were effective at enhancing methyl ketone titer: (1) chromosomal deletion of pgi (glucose-6-phosphate isomerase) to increase intracellular NADPH supply and (2) downregulation of CRP (cAMP receptor protein) expression by replacement of the native RBS with an RBS chosen based upon mutant library screening results. Combining these strategies resulted in the most favorable overall phenotypes for simultaneous glucose-xylose consumption without compromising methyl ketone titer at both 1 and 2% total sugar concentrations in shake flasks. This work demonstrated a strategy for engineering simultaneous utilization of C 6 and C 5 sugars in E. coli without sacrificing production of fatty acid-derived compounds.

  15. Heme oxygenase 1 improves glucoses metabolism and kidney histological alterations in diabetic rats

    Directory of Open Access Journals (Sweden)

    Ptilovanciv Ellen ON

    2013-01-01

    Full Text Available Abstract One important concern in the treatment of diabetes is the maintenance of glycemic levels and the prevention of diabetic nephropathy. Inducible heme oxygenase 1 (HO-1 is a rate-limiting enzyme thought to have antioxidant and cytoprotective roles. The goal of the present study was to analyze the effect of HO-1 induction in chronically hyperglycemic rats. The hyperglycemic rats were divided into two groups: one group, called STZ, was given a single injection of streptozotocin; and the other group was given a single streptozotocin injection as well as daily injections of hemin, an HO-1 inducer, over 60 days (STZ + HEME. A group of normoglycemic, untreated rats was used as the control (CTL. Body weight, diuresis, serum glucose levels, microalbuminuria, creatinine clearance rate, urea levels, sodium excretion, and lipid peroxidation were analyzed. Histological alterations and immunohistochemistry for HO-1 and inducible nitric oxide synthase (iNOS were assessed. After 60 days, the STZ group exhibited an increase in blood glucose, diuresis, urea, microalbuminuria, and sodium excretion. There was no weight gain, and there was a decrease in creatinine clearance in comparison to the CTL group. In the STZ + HEME group there was an improvement in the metabolic parameters and kidney function, a decrease in blood glucose, serum urea, and microalbuminuria, and an increase of creatinine clearance, in comparison to the STZ group. There was glomerulosclerosis, collagen deposition in the STZ rats and increase in iNOS and HO-1 expression. In the STZ + HEME group, the glomerulosclerosis and fibrosis was prevented and there was an increase in the expression of HO-1, but decrease in iNOS expression and lipid peroxidation. In conclusion, our data suggest that chronic induction of HO-1 reduces hyperglycemia, improves glucose metabolism and, at least in part, protects the renal tissue from hyperglycemic injury, possibly through the antioxidant

  16. Study of potential utility of new radiopharmaceuticals based on technetium-99m labeled derivative of glucose

    Science.gov (United States)

    Zeltchan, R.; Medvedeva, A.; Sinilkin, I.; Chernov, V.; Stasyuk, E.; Rogov, A.; Il'ina, E.; Larionova, L.; Skuridin, V.

    2016-08-01

    Purpose: to study the potential utility of 1-thio-D-glucose labeled with 99mTc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of 99mTc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with 99mTc was added to the vials with 3 million cells and incubated for 30 min at room temperature. After centrifugation of the vials with cells, the supernatant was removed. The radioactivity in vials with normal and tumor cells was then measured. In addition, the study included 40 mice of C57B1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25 MBq of 99mTc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 min. Results: when measuring the radioactivity of normal and malignant cells after incubation with 99mTc-1-thio-D-glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3 ± 0.15 MBq and 1.07 ± 0.6 MBq, respectively. All examined animals had increased accumulation of 99mTc-1-thio-D-glucose at the tumor site. The accumulation of 99mTc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that 99mTc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of 99mTc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.

  17. Study of potential utility of new radiopharmaceuticals based on technetium-99m labeled derivative of glucose

    Energy Technology Data Exchange (ETDEWEB)

    Zeltchan, R., E-mail: r.zelchan@yandex.ru; Medvedeva, A.; Sinilkin, I.; Chernov, V. [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation); Stasyuk, E.; Rogov, A.; Il’ina, E.; Larionova, L.; Skuridin, V. [Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation)

    2016-08-02

    Purpose: to study the potential utility of 1-thio-D-glucose labeled with {sup 99m}Tc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of {sup 99m}Tc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with {sup 99m}Tc was added to the vials with 3 million cells and incubated for 30 min at room temperature. After centrifugation of the vials with cells, the supernatant was removed. The radioactivity in vials with normal and tumor cells was then measured. In addition, the study included 40 mice of C57B1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25 MBq of {sup 99m}Tc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 min. Results: when measuring the radioactivity of normal and malignant cells after incubation with {sup 99m}Tc-1-thio-D-glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3 ± 0.15 MBq and 1.07 ± 0.6 MBq, respectively. All examined animals had increased accumulation of {sup 99m}Tc-1-thio-D-glucose at the tumor site. The accumulation of {sup 99m}Tc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that {sup 99m}Tc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of {sup 99m}Tc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.

  18. Circulating soluble CD36 is a novel marker of liver injury in subjects with altered glucose tolerance

    DEFF Research Database (Denmark)

    Fernández-Real, Jose-Manuel; Handberg, Aase; Ortega, Francisco

    2008-01-01

    ) and indicators of liver health. We evaluated a cohort of men from the general population (n=117). As expected, serum (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) were associated positively with body mass index (BMI) and age and negatively with SI (minimal model method). Circulating...... sCD36 was positively associated with ALT, AST and GGT in subjects with altered glucose tolerance, but not in those with normal glucose tolerance. The difference in the slope of the relationships was significant (P=.01). Age, BMI and triglycerides (but not sCD36) contributed independently to 29......% of ALT variance in subjects with normal glucose tolerance. In contrast, SI and sCD36 contributed independently to 39% of ALT variance in subjects with altered glucose tolerance. The correlation between ALT activity and sCD36 was confirmed in an independent, replication study. In summary, circulating s...

  19. Glucose alteration and insulin resistance in asymptomatic obese children and adolescents.

    Science.gov (United States)

    Assunção, Silvana Neves Ferraz de; Boa Sorte, Ney Christian Amaral; Alves, Crésio de Aragão Dantas; Mendes, Patricia S Almeida; Alves, Carlos Roberto Brites; Silva, Luciana Rodrigues

    2017-08-26

    Obesity is associated with the abnormal glucose metabolism preceding type 2 diabetes mellitus. Thus, further investigation on the prediction of this lethal outcome must be sought. The objective was the profile glycemic assessment of asymptomatic obese children and adolescents from Salvador, Brazil. A fasting venous blood sample was obtained from 90 consecutive obese individuals aged 8-18 years, of both sexes, for laboratory determinations of glycated hemoglobin, basal insulin, and the Homeostasis Model Assessment Insulin Resistance index. The clinical evaluation included weight, height, waist circumference, assessment of pubertal development, and acanthosis nigricans research. The body mass index/age indicator was used for the severity of overweight assessment. Glycemic alterations were evidenced clinically and biochemically, although these individuals had no complaints or symptoms related to blood sugar levels. Quantitative and qualitative variables were respectively expressed measures of central tendency/dispersion and simple/relative frequency, using the SPSS, version 20.0. A p-value <0.05 was considered significant. Notably, this study found a high prevalence of glucose and insulin disorders in asymptomatic obese children and adolescents. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  20. Impact of streptozotocin on altering normal glucose homeostasis during insulin testing in diabetic rats compared to normoglycemic rats

    Science.gov (United States)

    Qinna, Nidal A; Badwan, Adnan A

    2015-01-01

    Streptozotocin (STZ) is currently the most used diabetogenic agent in testing insulin and new antidiabetic drugs in animals. Due to the toxic and disruptive nature of STZ on organs, apart from pancreas, involved in preserving the body’s normal glucose homeostasis, this study aims to reassess the action of STZ in inducing different glucose response states in diabetic rats while testing insulin. Diabetic Sprague-Dawley rats induced with STZ were classified according to their initial blood glucose levels into stages. The effect of randomizing rats in such a manner was investigated for the severity of interrupting normal liver, pancreas, and kidney functions. Pharmacokinetic and pharmacodynamic actions of subcutaneously injected insulin in diabetic and nondiabetic rats were compared. Interruption of glucose homeostasis by STZ was challenged by single and repeated administrations of injected insulin and oral glucose to diabetic rats. In diabetic rats with high glucose (451–750 mg/dL), noticeable changes were seen in the liver and kidney functions compared to rats with lower basal glucose levels. Increased serum levels of recombinant human insulin were clearly indicated by a significant increase in the calculated maximum serum concentration and area under the concentration–time curve. Reversion of serum glucose levels to normal levels pre- and postinsulin and oral glucose administrations to STZ diabetic rats were found to be variable. In conclusion, diabetic animals were more responsive to insulin than nondiabetic animals. STZ was capable of inducing different levels of normal glucose homeostasis disruption in rats. Both pharmacokinetic and pharmacodynamic actions of insulin were altered when different initial blood glucose levels of STZ diabetic rats were selected for testing. Such findings emphasize the importance of selecting predefined and unified glucose levels when using STZ as a diabetogenic agent in experimental protocols evaluating new antidiabetic agents

  1. 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.)

  2. Oxygen glucose deprivation in rat hippocampal slice cultures results in alterations in carnitine homeostasis and mitochondrial dysfunction.

    Directory of Open Access Journals (Sweden)

    Thomas F Rau

    Full Text Available Mitochondrial dysfunction characterized by depolarization of mitochondrial membranes and the initiation of mitochondrial-mediated apoptosis are pathological responses to hypoxia-ischemia (HI in the neonatal brain. Carnitine metabolism directly supports mitochondrial metabolism by shuttling long chain fatty acids across the inner mitochondrial membrane for beta-oxidation. Our previous studies have shown that HI disrupts carnitine homeostasis in neonatal rats and that L-carnitine can be neuroprotective. Thus, this study was undertaken to elucidate the molecular mechanisms by which HI alters carnitine metabolism and to begin to elucidate the mechanism underlying the neuroprotective effect of L-carnitine (LCAR supplementation. Utilizing neonatal rat hippocampal slice cultures we found that oxygen glucose deprivation (OGD decreased the levels of free carnitines (FC and increased the acylcarnitine (AC: FC ratio. These changes in carnitine homeostasis correlated with decreases in the protein levels of carnitine palmitoyl transferase (CPT 1 and 2. LCAR supplementation prevented the decrease in CPT1 and CPT2, enhanced both FC and the AC∶FC ratio and increased slice culture metabolic viability, the mitochondrial membrane potential prior to OGD and prevented the subsequent loss of neurons during later stages of reperfusion through a reduction in apoptotic cell death. Finally, we found that LCAR supplementation preserved the structural integrity and synaptic transmission within the hippocampus after OGD. Thus, we conclude that LCAR supplementation preserves the key enzymes responsible for maintaining carnitine homeostasis and preserves both cell viability and synaptic transmission after OGD.

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

    Science.gov (United States)

    Nakagawa, Gen; Kouzuma, Atsushi; Hirose, Atsumi; Kasai, Takuya; Yoshida, Gen; Watanabe, Kazuya

    2015-01-01

    In bioelectrochemical systems, the electrode potential is an important parameter affecting the electron flow between electrodes and microbes and microbial metabolic activities. Here, we investigated the metabolic characteristics of a glucose-utilizing strain of engineered Shewanella oneidensis under electrode-respiring conditions in electrochemical reactors for gaining insight into how metabolic pathways in electrochemically active bacteria are affected by the electrode potential. When an electrochemical reactor was operated with its working electrode poised at +0.4 V (vs. an Ag/AgCl reference electrode), the engineered S. oneidensis strain, carrying a plasmid encoding a sugar permease and glucose kinase of Escherichia coli, generated current by oxidizing glucose to acetate and produced D-lactate as an intermediate metabolite. However, D-lactate accumulation was not observed when the engineered strain was grown with a working electrode poised at 0 V. We also found that transcription of genes involved in pyruvate and D-lactate metabolisms was upregulated at a high electrode potential compared with their transcription at a low electrode potential. These results suggest that the carbon catabolic pathway of S. oneidensis can be modified by controlling the potential of a working electrode in an electrochemical bioreactor.

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

    Directory of Open Access Journals (Sweden)

    Gen Nakagawa

    Full Text Available In bioelectrochemical systems, the electrode potential is an important parameter affecting the electron flow between electrodes and microbes and microbial metabolic activities. Here, we investigated the metabolic characteristics of a glucose-utilizing strain of engineered Shewanella oneidensis under electrode-respiring conditions in electrochemical reactors for gaining insight into how metabolic pathways in electrochemically active bacteria are affected by the electrode potential. When an electrochemical reactor was operated with its working electrode poised at +0.4 V (vs. an Ag/AgCl reference electrode, the engineered S. oneidensis strain, carrying a plasmid encoding a sugar permease and glucose kinase of Escherichia coli, generated current by oxidizing glucose to acetate and produced D-lactate as an intermediate metabolite. However, D-lactate accumulation was not observed when the engineered strain was grown with a working electrode poised at 0 V. We also found that transcription of genes involved in pyruvate and D-lactate metabolisms was upregulated at a high electrode potential compared with their transcription at a low electrode potential. These results suggest that the carbon catabolic pathway of S. oneidensis can be modified by controlling the potential of a working electrode in an electrochemical bioreactor.

  5. Utilization of glucose and UDPG by supprotoplasts of cotton fiber cells

    International Nuclear Information System (INIS)

    Gould, J.H.; Dugger, W.M.

    1984-01-01

    The authors have developed a subprotoplast system for cotton fiber cells isolated after initiation of secondary wall and cellulose synthesis. In the absence of a cell-free system for cellulose synthesis, protoplasts and subprotoplasts offer an opportunity to study cellulose synthesis as well as precursor utilization. In these systems, however, the incorporation of precursor is confused by an unknown mode of uptake from the culture medium. These studies were undertaken to clarify the uptake question. Results could corroborate a model of UDP-glucose utilization at the plasma membrane surface or uptake of an intact molecule. The cotton fiber subprotoplast system appears to synthesize a product characteristic of cellulose in enough quantity for further characterization, and may prove to be useful in studying some aspects of cellulose synthesis

  6. Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

    International Nuclear Information System (INIS)

    Liu, Yansong; Xu, Dan; Feng, Jianghua; Kou, Hao; Liang, Gai; Yu, Hong; He, Xiaohua; Zhang, Baifang; Chen, Liaobin; Magdalou, Jacques; Wang, Hui

    2012-01-01

    The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by 1 H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine ingestion

  7. Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yansong [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China); Feng, Jianghua, E-mail: jianghua.feng@xmu.edu.cn [Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071 (China); Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, 361005 (China); Kou, Hao; Liang, Gai [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Yu, Hong; He, Xiaohua; Zhang, Baifang; Chen, Liaobin [Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China)

    2012-07-15

    The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by {sup 1}H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine

  8. Taurine depresses cardiac contractility and enhances systemic heart glucose utilization in the cuttlefish, Sepia officinalis.

    Science.gov (United States)

    MacCormack, Tyson J; Callaghan, N I; Sykes, A V; Driedzic, W R

    2016-02-01

    Taurine is the most abundant amino acid in the blood of the cuttlefish, Sepia officinalis, where levels can exceed 200 mmol L(-1). In mammals, intracellular taurine modulates cardiac Ca(2+) handling and carbohydrate metabolism at much lower concentrations but it is not clear if it exerts similar actions in cephalopods. Blood Ca(2+) levels are high in cephalopods and we hypothesized that taurine would depress cardiac Ca(2+) flux and modulate contractility in systemic and branchial hearts of cuttlefish. Heart performance was assessed with an in situ perfused systemic heart preparation and contractility was evaluated using isometrically contracting systemic and branchial heart muscle rings. Stroke volume, cardiac output, and Ca(2+) sensitivity were significantly lower in systemic hearts perfused with supplemental taurine (100 mmol L(-1)) than in controls. In muscle ring preparations, taurine impaired relaxation at high contraction frequencies, an effect abolished by supra-physiological Ca(2+) levels. Taurine did not affect oxygen consumption in non-contracting systemic heart muscle, but extracellular glucose utilization was twice that of control preparations. Collectively, our results suggest that extracellular taurine depresses cardiac Ca(2+) flux and potentiates glucose utilization in cuttlefish. Variations in taurine levels may represent an important mechanism for regulating cardiovascular function and metabolism in cephalopods.

  9. Different training status may alter the continuous blood glucose kinetics in self-paced endurance running

    OpenAIRE

    SUZUKI, YOSHIO; SHIMIZU, TOMOMI; OTA, MAKOTO; HIRATA, RYUZO; SATO, KENJI; TAMURA, YOSHIFUMI; IMANISHI, AKIO; WATANABE, MASAYUKI; SAKURABA, KEISHOKU

    2015-01-01

    The main purpose of the systemic energy metabolism is to provide a source of energy, mainly glucose, for the brain; therefore, blood glucose levels would be expected to correlate with exercise performance. The individual training status may also affect the blood glucose levels. The aim of the present study was to assess the association between blood glucose levels and running velocity during prolonged running in athletes with different training statuses. Two female college athletes, a triathl...

  10. Dietary Capsaicin Improves Glucose Homeostasis and Alters the Gut Microbiota in Obese Diabetic ob/ob Mice

    Directory of Open Access Journals (Sweden)

    Jun-Xian Song

    2017-08-01

    Full Text Available Background: The effects of capsaicin on obesity and glucose homeostasis are still controversial and the mechanisms underlying these effects remain largely unknown. This study aimed to investigate the potential relationship between the regulation of obesity and glucose homeostasis by dietary capsaicin and the alterations of gut microbiota in obese diabetic ob/ob mice.Methods: The ob/ob mice were subjected to a normal, low-capsaicin (0.01%, or high-capsaicin (0.02% diet for 6 weeks, respectively. Obesity phenotypes, glucose homeostasis, the gut microbiota structure and composition, short-chain fatty acids, gastrointestinal hormones, and pro-inflammatory cytokines were measured.Results: Both the low- and high-capsaicin diets failed to prevent the increase in body weight, adiposity index, and Lee's obesity index. However, dietary capsaicin at both the low and high doses significantly inhibited the increase of fasting blood glucose and insulin levels. These inhibitory effects were comparable between the two groups. Similarly, dietary capsaicin resulted in remarkable improvement in glucose and insulin tolerance. In addition, neither the low- nor high-capsaicin diet could alter the α-diversity and β-diversity of the gut microbiota. Taxonomy-based analysis showed that both the low- and high-capsaicin diets, acting in similar ways, significantly increased the Firmicutes/Bacteroidetes ratio at the phylum level as well as increased the Roseburia abundance and decreased the Bacteroides and Parabacteroides abundances at the genus level. Spearman's correlation analysis revealed that the Roseburia abundance was negatively while the Bacteroides and Parabacteroides abundances were positively correlated to the fasting blood glucose level and area under the curve by the oral glucose tolerance test. Finally, the low- and high-capsaicin diets significantly increased the fecal butyrate and plasma total GLP-1 levels, but decreased plasma total ghrelin, TNF-α, IL-1

  11. Transient Congenital Hypothyroidism Alters Gene Expression of Glucose Transporters and Impairs Glucose Sensing Apparatus in Young and Aged Offspring Rats

    Directory of Open Access Journals (Sweden)

    Hanieh Gholami

    2017-10-01

    Full Text Available Background/Aims: Transient congenital hypothyroidism (TCH could disturb carbohydrate metabolism in adulthood. Aging is associated with increased risk of type 2 diabetes. This study aims to address effects of TCH on mRNA expressions of glucose transporters (GLUTs and glucokinase (GcK in islets and insulin target tissues of aged offspring rats. Methods: The TCH group received water containing 0.025% 6-propyl-2-thiouracil during gestation. Offspring from control and TCH groups (n=6 in each group were followed until month 19. Gene expressions of GLUTs and GcK were measured at months 3 and 19. Results: Compared to controls, aged TCH rats had higher GLUT4 expression in heart (4.88 fold and soleus (6.91 fold, while expression was lower in epididymal fat (12%. In TCH rats, GLUT2 and GcK expressions in islets were lower in young (12% and 10%, respectively and higher in aged (10.85 and 8.42 fold, respectively rats. In addition, liver GLUT2 and GcK expressions were higher in young (13.11 and 21.15 fold, respectively and lower in aged rats (44% and 5%, respectively. Conclusion: Thyroid hormone deficiency during fetal period impaired glucose sensing apparatus and changed glucose transporter expression in insulin-sensitive tissues of aged offspring rats. These changes may contribute to impaired carbohydrate metabolism.

  12. Transient Congenital Hypothyroidism Alters Gene Expression of Glucose Transporters and Impairs Glucose Sensing Apparatus in Young and Aged Offspring Rats.

    Science.gov (United States)

    Gholami, Hanieh; Jeddi, Sajad; Zadeh-Vakili, Azita; Farrokhfall, Khadije; Rouhollah, Fatemeh; Zarkesh, Maryam; Ghanbari, Mahboubeh; Ghasemi, Asghar

    2017-01-01

    Transient congenital hypothyroidism (TCH) could disturb carbohydrate metabolism in adulthood. Aging is associated with increased risk of type 2 diabetes. This study aims to address effects of TCH on mRNA expressions of glucose transporters (GLUTs) and glucokinase (GcK) in islets and insulin target tissues of aged offspring rats. The TCH group received water containing 0.025% 6-propyl-2-thiouracil during gestation. Offspring from control and TCH groups (n=6 in each group) were followed until month 19. Gene expressions of GLUTs and GcK were measured at months 3 and 19. Compared to controls, aged TCH rats had higher GLUT4 expression in heart (4.88 fold) and soleus (6.91 fold), while expression was lower in epididymal fat (12%). In TCH rats, GLUT2 and GcK expressions in islets were lower in young (12% and 10%, respectively) and higher in aged (10.85 and 8.42 fold, respectively) rats. In addition, liver GLUT2 and GcK expressions were higher in young (13.11 and 21.15 fold, respectively) and lower in aged rats (44% and 5%, respectively). Thyroid hormone deficiency during fetal period impaired glucose sensing apparatus and changed glucose transporter expression in insulin-sensitive tissues of aged offspring rats. These changes may contribute to impaired carbohydrate metabolism. © 2017 The Author(s). Published by S. Karger AG, Basel.

  13. Iron overload alters glucose homeostasis, causes liver steatosis, and increases serum triacylglycerols in rats.

    Science.gov (United States)

    Silva, Maísa; Silva, Marcelo E; de Paula, Heberth; Carneiro, Cláudia Martins; Pedrosa, Maria Lucia

    2008-06-01

    The objective of this study was to investigate the effect of iron overload with a hyperlipidemic diet on the histologic feature of hepatic tissue, the lipid and glycemic serum profiles, and the markers of oxidative damage and stress in a rat model. Twenty-four male Fischer rats, purchased from Experimental Nutrition Laboratory, Federal University of Ouro Preto, were assigned to 4 equal groups, 2 were fed a standard cholesterol-free diet (group C or control and CI or control with iron) containing 8.0% soybean oil and 2 were fed a hyperlipidemic diet (group H or hyperlipidemic and HI or hyperlipidemic with iron) containing 1.0% cholesterol and 25.0% soybean oil. A total of 50 mg of iron was administered to rats in groups CI and HI in 5 equal doses (1 every 3 weeks for a 16-week period) by intraperitoneal injections of 0.1 mL of iron dextran solution (100 g Fe(2+)/L; Sigma, St Louis, Mo). The other rats in groups C and H were treated in a similar manner but with sterile saline (0.1 mL). Irrespective of the diet, iron excess enhanced serum triacylglycerols (P .05) were observed in paraoxonase activities or in serum levels of free or total sulfhydryl radicals, malondialdehyde, or total antioxidants. The findings suggest that iron excess in the rat probably modifies lipid metabolism and, as a consequence, alters glucose homeostasis and increases the level of serum triacylglycerols but not of cholesterol.

  14. Whole grain products, fish and bilberries alter glucose and lipid metabolism in a randomized, controlled trial: the Sysdimet study.

    Directory of Open Access Journals (Sweden)

    Maria Lankinen

    Full Text Available Due to the growing prevalence of type 2 diabetes, new dietary solutions are needed to help improve glucose and lipid metabolism in persons at high risk of developing the disease. Herein we investigated the effects of low-insulin-response grain products, fatty fish, and berries on glucose metabolism and plasma lipidomic profiles in persons with impaired glucose metabolism.Altogether 106 men and women with impaired glucose metabolism and with at least two other features of the metabolic syndrome were included in a 12-week parallel dietary intervention. The participants were randomized into three diet intervention groups: (1 whole grain and low postprandial insulin response grain products, fatty fish three times a week, and bilberries three portions per day (HealthyDiet group, (2 Whole grain enriched diet (WGED group, which includes principally the same grain products as group (1, but with no change in fish or berry consumption, and (3 refined wheat breads (Control. Oral glucose tolerance, plasma fatty acids and lipidomic profiles were measured before and after the intervention. Self-reported compliance with the diets was good and the body weight remained constant. Within the HealthyDiet group two hour glucose concentration and area-under-the-curve for glucose decreased and plasma proportion of (n-3 long-chain PUFAs increased (False Discovery Rate p-values <0.05. Increases in eicosapentaenoic acid and docosahexaenoic acid associated curvilinearly with the improved insulin secretion and glucose disposal. Among the 364 characterized lipids, 25 changed significantly in the HealthyDiet group, including multiple triglycerides incorporating the long chain (n-3 PUFA.The results suggest that the diet rich in whole grain and low insulin response grain products, bilberries, and fatty fish improve glucose metabolism and alter the lipidomic profile. Therefore, such a diet may have a beneficial effect in the efforts to prevent type 2 diabetes in high risk

  15. Effects of hypopituitarism and growth hormone replacement therapy on the production and utilization of glucose in childhood.

    Science.gov (United States)

    Bougneres, P F; Artavia-Loria, E; Ferre, P; Chaussain, J L; Job, J C

    1985-12-01

    Glucose metabolism during fasting was investigated in 10 children aged 1.5 month-11.5 yr with deficiency of GH with or without other pituitary hormone deficiencies. After 10-16 h of fasting, mean plasma glucose was 56 +/- 4 (SEM) mg/dl, the result of decreased hepatic production of glucose (3.3 +/- 0.3 mg kg-1 min-1) insufficient to match glucose utilization (3.6 +/- 0.4 mg kg-1 min-1). The diminution of plasma glucose and of glucose production was similar whether ACTH deficiency was present (3.2 +/- mg kg-1 min-1) or not (3.5 +/- 0.6 mg kg-1 min-1). These results indicate that the lack of GH was the primary cause of hypoglycemia. Fasting plasma alanine (212 +/- 41 mumol/liter) and lactate (1222 +/- 136 mumol/liter), the main gluconeogenic substrates, were normal and did not correlate with the decrease of hepatic glucose release. Both plasma FFA (552 +/- 35 microM) and beta-hydroxybutyrate (654 +/- 158 microM) were in the low normal range, and neither correlated with the rate of glucose utilization. hGH replacement therapy resulted in a normalization of fasting plasma glucose concentration (78.5 +/- 6 mg/dl, P less than 0.005) and hepatic glucose production (6.1 +/- 1.2 mg kg-1 min-1). No significant changes occurred in the plasma concentrations of gluconeogenic or lipid substrates. These results, together with the known stimulatory effects of GH on carbohydrate-induced insulin secretion and storage of hepatic glycogen, suggest that the changes in glucose production in untreated and GH treated patients reflect the degree of hepatic glycogen replenishment.

  16. Different training status may alter the continuous blood glucose kinetics in self-paced endurance running.

    Science.gov (United States)

    Suzuki, Yoshio; Shimizu, Tomomi; Ota, Makoto; Hirata, Ryuzo; Sato, Kenji; Tamura, Yoshifumi; Imanishi, Akio; Watanabe, Masayuki; Sakuraba, Keishoku

    2015-09-01

    The main purpose of the systemic energy metabolism is to provide a source of energy, mainly glucose, for the brain; therefore, blood glucose levels would be expected to correlate with exercise performance. The individual training status may also affect the blood glucose levels. The aim of the present study was to assess the association between blood glucose levels and running velocity during prolonged running in athletes with different training statuses. Two female college athletes, a triathlete and a tennis player, ran a course that was 247.4 m in circumference for 5 h while wearing a continuous glucose monitoring system. Blood was obtained at time-points of -1, 1, 3 and 5 h. The athletes had free access to food and fluids throughout the run. The athletes ran at almost the same pace without a sudden decrease in pace. The blood glucose levels increased and remained high in the triathlete, whereas the tennis player remained hypoglycemic throughout the run. Carbohydrate ingestion did not affect the blood glucose levels. The magnitude of hormonal changes, e.g. insulin, adrenaline and cortisol, was greater in the tennis player. The blood glucose concentration did not correlate with the running velocity or the carbohydrate ingestion; however, a discrepancy in blood glucose transition was observed between the triathlete and the tennis player, indicating a possible association between the adaptation to endurance exercise and the blood glucose kinetics during prolonged running.

  17. Impact of streptozotocin on altering normal glucose homeostasis during insulin testing in diabetic rats compared to normoglycemic rats

    Directory of Open Access Journals (Sweden)

    Qinna NA

    2015-05-01

    altered when different initial blood glucose levels of STZ diabetic rats were selected for testing. Such findings emphasize the importance of selecting predefined and unified glucose levels when using STZ as a diabetogenic agent in experimental protocols evaluating new antidiabetic agents and insulin delivery systems. Keywords: protein delivery, animal model, diabetes mellitus, experimental, antidiabetic agents, streptozotocin 

  18. Sleep duration and sleep quality are associated differently with alterations of glucose homeostasis

    DEFF Research Database (Denmark)

    Byberg, Stine; Hansen, Anne-Louise Smidt; Christensen, Dirk Lund

    2012-01-01

    Abstract Aims  Studies suggest that inadequate sleep duration and poor sleep quality increase the risk of impaired glucose regulation and diabetes. However, associations with specific markers of glucose homeostasis are less well explained. The objective of this study was to explore possible...... associations of sleep duration and sleep quality with markers of glucose homeostasis and glucose tolerance status in a healthy population-based study sample. Methods  The study comprised 771 participants from the Danish, population-based cross-sectional ‘Health2008’ study. Sleep duration and sleep quality were......), the homeostasis model assessment of β-cell function and glucose tolerance status. Associations of sleep duration and sleep quality with markers of glucose homeostasis and tolerance were analysed by multiple linear and logistic regression. Results  A 1-h increment in sleep duration was associated with a 0.3 mmol...

  19. Extracellular matrix production by nucleus pulposus and bone marrow stem cells in response to altered oxygen and glucose microenvironments.

    Science.gov (United States)

    Naqvi, Syeda M; Buckley, Conor T

    2015-12-01

    Bone marrow (BM) stem cells may be an ideal source of cells for intervertebral disc (IVD) regeneration. However, the harsh biochemical microenvironment of the IVD may significantly influence the biological and metabolic vitality of injected stem cells and impair their repair potential. This study investigated the viability and production of key matrix proteins by nucleus pulposus (NP) and BM stem cells cultured in the typical biochemical microenvironment of the IVD consisting of altered oxygen and glucose concentrations. Culture-expanded NP cells and BM stem cells were encapsulated in 1.5% alginate and ionically crosslinked to form cylindrical hydrogel constructs. Hydrogel constructs were maintained under different glucose concentrations (1, 5 and 25 mM) and external oxygen concentrations (5 and 20%). Cell viability was measured using the Live/Dead® assay and the production of sulphated glycosaminoglycans (sGAG), and collagen was quantified biochemically and histologically. For BM stem cells, IVD-like micro-environmental conditions (5 mM glucose and 5% oxygen) increased the accumulation of sGAG and collagen. In contrast, low glucose conditions (1 mM glucose) combined with 5% external oxygen concentration promoted cell death, inhibiting proliferation and the accumulation of sGAG and collagen. NP-encapsulated alginate constructs were relatively insensitive to oxygen concentration or glucose condition in that they accumulated similar amounts of sGAG under all conditions. Under IVD-like microenvironmental conditions, NP cells were found to have a lower glucose consumption rate compared with BM cells and may in fact be more suitable to adapt and sustain the harsh microenvironmental conditions. Considering the highly specialised microenvironment of the central NP, these results indicate that IVD-like concentrations of low glucose and low oxygen are critical and influential for the survival and biological behaviour of stem cells. Such findings may promote and accelerate

  20. Effect of mercury and organomercurials on cellular glucose utilization: a study using resting mercury-resistant yeast cells.

    Science.gov (United States)

    Ghosh, S K; Chaudhuri, J; Gachhui, R; Mandal, A; Ghosh, S

    2007-02-01

    Mercury compounds are highly toxic to all types of living cells. Isolated yeast strains of Rhodotorula rubra showed high and low resistance pattern towards mercury and organomercurial compounds. To investigate the basis of differential sensitivity of these two types of strains, glucose utilization was measured in the presence of mercury compounds. Glucose utilization process remained unaffected in resting cells of highly Hg(2+)-resistant strain in the presence of HgCl(2) but not in the presence of phenylmercuric acetate and thimerosal. However, HgCl(2) significantly affected glucose utilization in the case of low-resistant cells. The Hg-retaining ability of the cell wall of highly Hg(2+)-resistant yeast strain was greater than that of the weakly Hg(2+)-resistant strain. The spheroplast-bound Hg(2+) was also significantly less in the highly Hg(2+)-resistant strain than in the weakly Hg(2+)-resistant strain. Glucose uptake machinery was not affected in the presence of toxic metal ions in the case of high-resistant strains. But in the case of low Hg(2+)-resistant strain, glucose transport system may be affected either by inactivation of sensor proteins containing -SH group associated with glucose uptake. Cell wall of mercury-resistant yeast cells may play an important role in heavy metal bioremediation process.

  1. Altered glucose metabolism in juvenile myoclonic epilepsy: a PET study with statistical parametric mapping

    Energy Technology Data Exchange (ETDEWEB)

    Lim, G. C.; Kim, J. H.; Kang, J. G.; Kim, J. S.; Yeo, J. S.; Lee, S. A.; Moon, D. H [Asan Medical Center, Seoul (Korea, Republic of)

    2004-07-01

    Juvenile myoclonic epilepsy (JME) is a hereditary, age-dependent epilepsy syndrome, characterized by myoclonic jerks on awakening and generalized tonic-clonic seizures. Although there have been considerable studies on the mechanism to elucidate pathogenesis of JME, the accurate pathogenesis of JME remains obscure. The aim of this study was to investigate alterations of cerebral glucose metabolism in patients with JME. We studied 16 JME patients (Mean age: 22 yrs, M/F: 9/7) with brain FDG-PET and simultaneous EEG recording. On the basis of the number of generalized spike-and-wave (GSW) discharges on the 30 min EEG recording after the injection of FDG (370MBq), we classified patients into two groups (patients in group A had 10 or more GSW and group B. 9 or less). We applied the automated and objective technique of statistical parametric mapping (SPM) to the analysis of FDG-PET to determine the significant hyper- and hypometabolic regions compared with those of 19 age matched normal control subjects. We found significant hypermetabolic regions in bilateral thalamus and central portion of upper brainstem in 16 patients with JME at a statistical threshold of uncorrected P < 0.05. These changes were also shown in group A (n=8), but not in group B (n=8). Additionally, we found significant hypometabolism in bilateral, widespread cortical regions in 16 patients with JME at a threshold of uncorrected P < 0.01. Similar hypometabolic patterns were also observed in both group A and group B, being more prominent in group A. This study provides evidence for the key role of the thalamus and brainstem reticular activating system in generating spontaneous GSW discharge, which is considered as a fundamental pathogenesis underlying JME. This study also suggests that patients with JME might suffer from subtle abnormalities of cognitive and executive cortical functions.

  2. Alterations in glucose metabolism in non-endocrine disease: potential implication for wasting

    NARCIS (Netherlands)

    Sauerwein, H. P.; Romijn, J. A.

    2001-01-01

    Diseases like sepsis, AIDS and cancer can induce an increase in endogenous glucose production. Sepsis and cancer induce insulin resistance whereas increased insulin sensitivity is found in AIDS. Non-oxidative glucose disposal is increased in sepsis and cancer but normal in AIDS. These differences in

  3. RNA-Seq of Kaposi's sarcoma reveals alterations in glucose and lipid metabolism.

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    For Yue Tso

    2018-01-01

    Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is the etiologic agent of Kaposi's sarcoma (KS. It is endemic in a number of sub-Saharan African countries with infection rate of >50%. The high prevalence of HIV-1 coupled with late presentation of advanced cancer staging make KS the leading cancer in the region with poor prognosis and high mortality. Disease markers and cellular functions associated with KS tumorigenesis remain ill-defined. Several studies have attempted to investigate changes of the gene profile with in vitro infection of monoculture models, which are not likely to reflect the cellular complexity of the in vivo lesion environment. Our approach is to characterize and compare the gene expression profile in KS lesions versus non-cancer tissues from the same individual. Such comparisons could identify pathways critical for KS formation and maintenance. This is the first study that utilized high throughput RNA-seq to characterize the viral and cellular transcriptome in tumor and non-cancer biopsies of African epidemic KS patients. These patients were treated anti-retroviral therapy with undetectable HIV-1 plasma viral load. We found remarkable variability in the viral transcriptome among these patients, with viral latency and immune modulation genes most abundantly expressed. The presence of KSHV also significantly affected the cellular transcriptome profile. Specifically, genes involved in lipid and glucose metabolism disorder pathways were substantially affected. Moreover, infiltration of immune cells into the tumor did not prevent KS formation, suggesting some functional deficits of these cells. Lastly, we found only minimal overlaps between our in vivo cellular transcriptome dataset with those from in vitro studies, reflecting the limitation of in vitro models in representing tumor lesions. These findings could lead to the identification of diagnostic and therapeutic markers for KS, and will provide bases for further mechanistic

  4. Simultaneous utilization of glucose, xylose and arabinose in the presence of acetate by a consortium of Escherichia coli strains

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    Xia Tian

    2012-06-01

    Full Text Available Abstract Background The efficient microbial utilization of lignocellulosic hydrolysates has remained challenging because this material is composed of multiple sugars and also contains growth inhibitors such as acetic acid (acetate. Using an engineered consortium of strains derived from Escherichia coli C and a synthetic medium containing acetate, glucose, xylose and arabinose, we report on both the microbial removal of acetate and the subsequent simultaneous utilization of the sugars. Results In a first stage, a strain unable to utilize glucose, xylose and arabinose (ALS1392, strain E. coli C ptsG manZ glk crr xylA araA removed 3 g/L acetate within 30 hours. In a subsequent second stage, three E. coli strains (ALS1370, ALS1371, ALS1391, which are each engineered to utilize only one sugar, together simultaneously utilized glucose, xylose and arabinose. The effect of non-metabolizable sugars on the metabolism of the target sugar was minimal. Additionally the deletions necessary to prevent the consumption of one sugar only minimally affected the consumption of a desired sugar. For example, the crr deletion necessary to prevent glucose consumption reduced xylose and arabinose utilization by less than 15% compared to the wild-type. Similarly, the araA deletion used to exclude arabinose consumption did not affect xylose- and glucose-consumption. Conclusions Despite the modest reduction in the overall rate of sugar consumption due to the various deletions that were required to generate the consortium of strains, the approach constitutes a significant improvement in any single-organism approach to utilize sugars found in lignocellulosic hydrolysate in the presence of acetate.

  5. Alterations in basal glucose metabolism during late pregnancy in the conscious dog.

    Science.gov (United States)

    Connolly, C C; Holste, L C; Aglione, L N; Neal, D W; Lacy, D B; Smith, M S; Diamond, M P; Cherrington, A D; Chiasson, J L

    2000-11-01

    We assessed basal glucose metabolism in 16 female nonpregnant (NP) and 16 late-pregnant (P) conscious, 18-h-fasted dogs that had catheters inserted into the hepatic and portal veins and femoral artery approximately 17 days before the experiment. Pregnancy resulted in lower arterial plasma insulin (11 +/- 1 and 4 +/- 1 microU/ml in NP and P, respectively, P dog is not accompanied by changes in the absolute rates of gluconeogenesis or glycogenolysis. Rather, repartitioning of the glucose released from glycogen is responsible for the increase in hepatic glucose production.

  6. Reduction in muscle glycogen and protein utilization with glucose feeding during exercise.

    NARCIS (Netherlands)

    Hamont, D. van; Harvey, C.R.; Massicotte, D.; Frew, R.; Peronnet, F.; Rehrer, N.J.

    2005-01-01

    Effects of feeding glucose on substrate metabolism during cycling were studied. Trained (60.0 +/- 1.9 mL x kg(-1) x min(-1)) males (N = 5) completed two 75 min, 80% VO(2max) trials: 125 g 13(C)-glucose CHO); 13(C)-glucose tracer, 10 g (C). During warm-up (30 min 30% VO2max) 2 . 2 g 13(C)-glucose was

  7. Duodenal and ileal glucose infusions differentially alter gastrointestinal peptides, appetite response, and food intake: a tube feeding study.

    Science.gov (United States)

    Poppitt, Sally D; Shin, Hyun Sang; McGill, Anne-Thea; Budgett, Stephanie C; Lo, Kim; Pahl, Malcolm; Duxfield, Janice; Lane, Mark; Ingram, John R

    2017-09-01

    Background: Activation of the ileal brake through the delivery of nutrients into the distal small intestine to promote satiety and suppress food intake provides a new target for weight loss. Evidence is limited, with support from naso-ileal lipid infusion studies. Objective: The objective of the study was to investigate whether glucose infused into the duodenum and ileum differentially alters appetite response, food intake, and secretion of satiety-related gastrointestinal peptides. Design: Fourteen healthy male participants were randomly assigned to a blinded 4-treatment crossover, with each treatment of single-day duration. On the day before the intervention (day 0), a 380-cm multilumen tube (1.75-mm diameter) with independent port access to the duodenum and ileum was inserted, and position was confirmed by X-ray. Subsequently (days 1-4), a standardized breakfast meal was followed midmorning by a 90-min infusion of isotonic glucose (15 g, 235 kJ) or saline to the duodenum or ileum. Appetite ratings were assessed with the use of visual analog scales (VASs), blood samples collected, and ad libitum energy intake (EI) measured at lunch, afternoon snack, and dinner. Results: Thirteen participants completed the 4 infusion days. There was a significant effect of nutrient infused and site (treatment × time, P lunch compared with glucose-to-duodenum [-22%, -988 ± 379 kJ (mean ± SEM), Tukey's post hoc, P small intestine elicits different outcomes. Glucose infusion to the ileum increased GLP-1 and PYY secretion, suppressed aspects of VAS-rated appetite, and decreased ad libitum EI at a subsequent meal. Although glucose to the duodenum also suppressed appetite ratings, eating behavior was not altered. This trial was registered at www.anzctr.org.au as ACTRN12612000429853. © 2017 American Society for Nutrition.

  8. Early alterations in soleus GLUT-4, glucose transport, and glycogen in voluntary running rats

    Science.gov (United States)

    Henriksen, Erik J.; Halseth, Amy E.

    1994-01-01

    Voluntary wheel running (WR) by juvenile female rats was used as a noninterventional model of soleus muscle functional overload to study the regulation of insulin-stimulated glucose transport activity by the glucose transporter (GLUT-4 isoform) protein level and glycogen concentration. Soleus total protein content was significantly greater (+18%;P greater than 0.05) than in age-matched controls after 1 wk of WR, and this hypertrophic response continued in weeks 2-4 (+24-32%). GLUT-4 protein was 39% greater than in controls in 1-wk WR soleus, and this adaptation was accompanied by a similar increase in in vitro insulin-stimulated glucose transport activity(+29%). After 2 and 4 wk of WR, however, insulin-stimulated glucose transport activity had returned to control levels, despite a continued elevation (+25-28%) of GLUT-4 protein. At these two time points, glycogen concentration was significantly enhanced in WR soleus (+21-42%), which coincided with significant reductions in glycogen synthase activity ratios (-23 to-41%). These results indicate that, in this model of soleus muscle functional overload, the GLUT-4 protein level may initially regulate insulin-stimulated glucose transport activity in the absence of changes in other modifying factors. However,this regulation of glucose transport activity by GLUT-4 protein may be subsequently overridden by elevated glycogen concentration.

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

    Science.gov (United States)

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

    2017-11-04

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

  10. INSL5-deficient mice display an alteration in glucose homeostasis and an impaired fertility.

    Science.gov (United States)

    Burnicka-Turek, Ozanna; Mohamed, Belal A; Shirneshan, Katayoon; Thanasupawat, Thatchawan; Hombach-Klonisch, Sabine; Klonisch, Thomas; Adham, Ibrahim M

    2012-10-01

    Insulin-like factor 5 (INSL5), a member of the insulin superfamily, is expressed in the colorectum and hypothalamus. To facilitate studies into the role of INSL5, we generated Insl5(-/-) mice by gene targeting. Insl5(-/-) mice were born in the expected Mendelian ratio, reached normal body weight, but displayed impaired male and female fertility that are due to marked reduction in sperm motility and irregular length of the estrous cycle. Furthermore, Insl5(-/-) mice showed impairment in glucose homeostasis with characteristic elevation of serum glucose levels at an advanced age. Glucose and insulin tolerance tests revealed that the increased blood glucose in Insl5(-/-) mice was due to glucose intolerance resulting from reduced insulin secretion. Morphometric and immunohistological analyses revealed that the Insl5(-/-) mice had markedly reduced average islets area and β-cell numbers. Furthermore, immunohistochemistry showed the expression of INSL5 in enteroendocrine cells in the colorectal epithelium and the presence of its putative receptor relaxin family peptide receptor 4 in pancreatic islet cells. These results suggest the potential role of INSL5 signaling in the regulation of insulin secretion and β-cell homeostasis.

  11. Altered glucose homeostasis and hepatic function in obese mice deficient for both kinin receptor genes.

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    Carlos C Barros

    Full Text Available The Kallikrein-Kinin System (KKS has been implicated in several aspects of metabolism, including the regulation of glucose homeostasis and adiposity. Kinins and des-Arg-kinins are the major effectors of this system and promote their effects by binding to two different receptors, the kinin B2 and B1 receptors, respectively. To understand the influence of the KKS on the pathophysiology of obesity and type 2 diabetes (T2DM, we generated an animal model deficient for both kinin receptor genes and leptin (obB1B2KO. Six-month-old obB1B2KO mice showed increased blood glucose levels. Isolated islets of the transgenic animals were more responsive to glucose stimulation releasing greater amounts of insulin, mainly in 3-month-old mice, which was corroborated by elevated serum C-peptide concentrations. Furthermore, they presented hepatomegaly, pronounced steatosis, and increased levels of circulating transaminases. This mouse also demonstrated exacerbated gluconeogenesis during the pyruvate challenge test. The hepatic abnormalities were accompanied by changes in the gene expression of factors linked to glucose and lipid metabolisms in the liver. Thus, we conclude that kinin receptors are important for modulation of insulin secretion and for the preservation of normal glucose levels and hepatic functions in obese mice, suggesting a protective role of the KKS regarding complications associated with obesity and T2DM.

  12. Effect of feeding garlic leaves on rumen fermentation, methane emission, plasma glucose kinetics, and nitrogen utilization in sheep.

    Science.gov (United States)

    Panthee, Arvinda; Matsuno, Ayana; Al-Mamun, Mohammad; Sano, Hiroaki

    2017-01-01

    Garlic and its constituents are reported to have been effective in reducing methane emission and also influence glucose metabolism in body; however, studies in ruminants using garlic leaves are scarce. Garlic leaves contain similar compounds as garlic bulbs, but are discarded in field after garlic bulb harvest. We speculate that feeding garlic leaves might show similar effect as garlic constituents in sheep and could be potential animal feed supplement. Thus, we examined the effect of freeze dried garlic leaves (FDGL) on rumen fermentation, methane emission, plasma glucose kinetics and nitrogen utilization in sheep. Six sheep were fed Control diet (mixed hay and concentrate (60:40)) or FDGL diet (Control diet supplemented with FDGL at 2.5 g/kg BW 0.75 of sheep) using a crossover design. Methane gas emission was measured using open-circuit respiratory chamber. Plasma glucose turnover rate was measured using isotope dilution technique of [U- 13 C]glucose. Rumen fluid, feces and urine were collected to measure rumen fermentation characteristics and nitrogen utilization. No significant difference in rumen fermentation parameters was noticed except for rumen ammonia tended to be higher (0.05 Methane emission per kg dry matter ingested and methane emission per kg dry matter digested were lower ( P  methane emission, glucose turnover rate and microbial nitrogen supply, further studies at higher dose would be necessary to conclude the merit of FDGL as supplement in ruminant feedstuff.

  13. Sortilin 1 knockout alters basal adipose glucose metabolism but not diet-induced obesity in mice.

    Science.gov (United States)

    Li, Jibiao; Matye, David J; Wang, Yifeng; Li, Tiangang

    2017-04-01

    Sortilin 1 (Sort1) is a trafficking receptor that has been implicated in the regulation of plasma cholesterol in humans and mice. Here, we use metabolomics and hyperinsulinemic-euglycemic clamp approaches to obtain further understanding of the in vivo effects of Sort1 deletion on diet-induced obesity as well as on adipose lipid and glucose metabolism. Results show that Sort1 knockout (KO) does not affect Western diet-induced obesity nor adipose fatty acid and ceramide concentrations. Under the basal fasting state, chow-fed Sort1 KO mice have decreased adipose glycolytic metabolites, but Sort1 deletion does not affect insulin-stimulated tissue glucose uptake during the insulin clamp. These results suggest that Sort1 loss-of-function in vivo does not affect obesity development, but differentially modulates adipose glucose metabolism under fasting and insulin-stimulated states. © 2017 Federation of European Biochemical Societies.

  14. Alterations of fasting glucose and fat metabolism in intrauterine growth-retarded newborn dogs.

    Science.gov (United States)

    Kliegman, R M

    1989-03-01

    Maternal nutritional deprivation resulted in reduced fetal weight at term gestation (251 +/- 7 vs. 277 +/- 7 g, P less than 0.01) in newborn dogs. Growth-retarded pups developed lower blood glucose levels after 3, 6, and 9 h of neonatal fasting, reduced plasma levels of free fatty acids (FFA) at 9 and 24 h, and lower ketone bodies at 24 h compared with age-matched newborn control pups. Systemic rates of palmitate and alanine turnover were not affected, but systemic glucose turnover was reduced for 3-9 h after birth. The rate of alanine incorporation into glucose from 3 to 9 h was also reduced in growth-retarded pups compared with timed controls. Paradoxically, the rate of incorporation of palmitate into triglycerides was augmented in the smaller growth-retarded pups. Hepatic glycogen content was reduced at every time in the study among growth-retarded pups, whereas the rates of glycogenolysis between birth and 24 h were equivalent in the two pup groups. In contrast, hepatic triglyceride levels were augmented throughout the study in pups with growth retardation. Maternal starvation and lower glucose levels resulted in a lower hepatic energy charge, and augmented cytoplasmic and mitochondrial NAD-to-NADH ratios in intrauterine growth-retarded pups. These data suggest that intrauterine growth retardation in dogs results in fasting neonatal hypoglycemia that is due in part to reduced systemic glucose production. We speculate that reduced rates of gluconeogenesis from alanine and reduced oxidation of alternate fuels such as FFA contribute to hypoglycemia. FFA recycling to triglyceride synthesis rather than oxidative pathways may contribute to the observed reduction of circulating glucose levels.

  15. CD14 deficiency impacts glucose homeostasis in mice through altered adrenal tone.

    Directory of Open Access Journals (Sweden)

    James L Young

    Full Text Available The toll-like receptors comprise one of the most conserved components of the innate immune system, signaling the presence of molecules of microbial origin. It has been proposed that signaling through TLR4, which requires CD14 to recognize bacterial lipopolysaccharide (LPS, may generate low-grade inflammation and thereby affect insulin sensitivity and glucose metabolism. To examine the long-term influence of partial innate immune signaling disruption on glucose homeostasis, we analyzed knockout mice deficient in CD14 backcrossed into the diabetes-prone C57BL6 background at 6 or 12 months of age. CD14-ko mice, fed either normal or high-fat diets, displayed significant glucose intolerance compared to wild type controls. They also displayed elevated norepinephrine urinary excretion and increased adrenal medullary volume, as well as an enhanced norepinephrine secretory response to insulin-induced hypoglycemia. These results point out a previously unappreciated crosstalk between innate immune- and sympathoadrenal- systems, which exerts a major long-term effect on glucose homeostasis.

  16. Dietary patterns in men and women are simultaneously determinants of altered glucose metabolism and bone metabolism.

    Science.gov (United States)

    Langsetmo, Lisa; Barr, Susan I; Dasgupta, Kaberi; Berger, Claudie; Kovacs, Christopher S; Josse, Robert G; Adachi, Jonathan D; Hanley, David A; Prior, Jerilynn C; Brown, Jacques P; Morin, Suzanne N; Davison, Kenneth S; Goltzman, David; Kreiger, Nancy

    2016-04-01

    We hypothesized that diet would have direct effects on glucose metabolism with direct and indirect effects on bone metabolism in a cohort of Canadian adults. We assessed dietary patterns (Prudent [fruit, vegetables, whole grains, fish, and legumes] and Western [soft drinks, potato chips, French fries, meats, and desserts]) from a semiquantitative food frequency questionnaire. We used fasting blood samples to measure glucose, insulin, homeostatic model assessment insulin resistance (HOMA-IR), 25-hydroxyvitamin D (25OHD), parathyroid hormone, bone-specific alkaline phosphatase (a bone formation marker), and serum C-terminal telopeptide (CTX; a bone resorption marker). We used multivariate regression models adjusted for confounders and including/excluding body mass index. In a secondary analysis, we examined relationships through structural equations models. The Prudent diet was associated with favorable effects on glucose metabolism (lower insulin and HOMA-IR) and bone metabolism (lower CTX in women; higher 25OHD and lower parathyroid hormone in men). The Western diet was associated with deleterious effects on glucose metabolism (higher glucose, insulin, and HOMA-IR) and bone metabolism (higher bone-specific alkaline phosphatase and lower 25OHD in women; higher CTX in men). Body mass index adjustment moved point estimates toward the null, indicating partial mediation. The structural equation model confirmed the hypothesized linkage with strong effects of Prudent and Western diet on metabolic risk, and both direct and indirect effects of a Prudent diet on bone turnover. In summary, a Prudent diet was associated with lower metabolic risk with both primary and mediated effects on bone turnover, suggesting that it is a potential target for reducing fracture risk. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Modified prokaryotic glucose isomerase enzymes with altered pH activity profiles

    NARCIS (Netherlands)

    Lambeir, Anne-Marie; Lasters, Ignace; Mrabet, Nadir; Quax, Wim; Van Der Laan, Jan M.; Misset, Onno

    1994-01-01

    A method for selecting amino acid residues is disclosed which upon replacement will give rise to an enzyme with an altered pH optimum. The method is specific for metalloenzymes which are inactivated at low pH due to the dissociation of the metal ions. The method is based on altering the pKa of the

  18. Sepsis does not alter red blood cell glucose metabolism or Na+ concentration: A 2H-, 23Na-NMR study

    International Nuclear Information System (INIS)

    Hotchkiss, R.S.; Song, S.K.; Ling, C.S.; Ackerman, J.J.; Karl, I.E.

    1990-01-01

    The effects of sepsis on intracellular Na+ concentration ([Na+]i) and glucose metabolism were examined in rat red blood cells (RBCs) by using 23Na- and 2H-nuclear magnetic resonance (NMR) spectroscopy. Sepsis was induced in 15 halothane-anesthetized female Sprague-Dawley rats by using the cecal ligation and perforation technique; 14 control rats underwent cecal manipulation without ligation. The animals were fasted for 36 h, but allowed free access to water. At 36 h postsurgery, RBCs were examined by 23Na-NMR by using dysprosium tripolyphosphate as a chemical shift reagent. Human RBCs from 17 critically ill nonseptic patients and from 7 patients who were diagnosed as septic were also examined for [Na+]i. Five rat RBC specimens had [Na+]i determined by both 23Na-NMR and inductively coupled plasma-atomic emission spectroscopy (ICP-AES). For glucose metabolism studies, RBCs from septic and control rats were suspended in modified Krebs-Henseleit buffer containing [6,6-2H2]glucose and examined by 2H-NMR. No significant differences in [Na+]i or glucose utilization were found in RBCs from control or septic rats. There were no differences in [Na+]i in the two groups of patients. The [Na+]i determined by NMR spectroscopy agreed closely with measurements using ICP-AES and establish that 100% of the [Na+]i of the RBC is visible by NMR. Glucose measurements determined by 2H-NMR correlated closely (correlation coefficient = 0.93) with enzymatic analysis. These studies showed no evidence that sepsis disturbed RBC membrane function or metabolism

  19. Global loss of bmal1 expression alters adipose tissue hormones, gene expression and glucose metabolism.

    Directory of Open Access Journals (Sweden)

    David John Kennaway

    Full Text Available The close relationship between circadian rhythm disruption and poor metabolic status is becoming increasingly evident, but role of adipokines is poorly understood. Here we investigated adipocyte function and the metabolic status of mice with a global loss of the core clock gene Bmal1 fed either a normal or a high fat diet (22% by weight. Bmal1 null mice aged 2 months were killed across 24 hours and plasma adiponectin and leptin, and adipose tissue expression of Adipoq, Lep, Retn and Nampt mRNA measured. Glucose, insulin and pyruvate tolerance tests were conducted and the expression of liver glycolytic and gluconeogenic enzyme mRNA determined. Bmal1 null mice displayed a pattern of increased plasma adiponectin and plasma leptin concentrations on both control and high fat diets. Bmal1 null male and female mice displayed increased adiposity (1.8 fold and 2.3 fold respectively on the normal diet, but the high fat diet did not exaggerate these differences. Despite normal glucose and insulin tolerance, Bmal1 null mice had increased production of glucose from pyruvate, implying increased liver gluconeogenesis. The Bmal1 null mice had arrhythmic clock gene expression in epigonadal fat and liver, and loss of rhythmic transcription of a range of metabolic genes. Furthermore, the expression of epigonadal fat Adipoq, Retn, Nampt, AdipoR1 and AdipoR2 and liver Pfkfb3 mRNA were down-regulated. These results show for the first time that global loss of Bmal1, and the consequent arrhythmicity, results in compensatory changes in adipokines involved in the cellular control of glucose metabolism.

  20. Altered glucose disposition and insulin sensitivity in peri-pubertal first-degree relatives of women with polycystic ovary syndrome

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    Raissouni Nouhad

    2012-05-01

    Full Text Available Abstract Background First-degree relatives (FDRs of women with PCOS are at increased risk for impaired insulin sensitivity and diabetes mellitus. Glucose tolerant FDR have evidence of insulin resistance and hyperinsulinemia prior to emergence of frank PCOS. Aim To study insulin dynamics parameters in the early adolescent FDR of women with PCOS. Methods This is a cross-sectional study involving 18 adolescents whose mothers or sisters had been diagnosed with PCOS and 21 healthy, age-matched control adolescents without FDR. Subjects underwent anthropometric measurements, steroid profiling and frequently sampled Intravenous Glucose Tolerance Test (IVGTT, Homeostasis Model Assessment (HOMA index, Glucose Disposal Index (GDI, Acute Insulin Response (AIR and Quantitative insulin sensitivity check index (QUICKI were derived from IVGTT results. Results FDRs showed significantly higher mean HOMA and lower GDI. There were no differences in mean age or BMI Z-score between the cohorts. No differences in sex steroids or AIR were identified between groups. Conclusion Female adolescent FDR of women with PCOS have higher HOMA index and lower QUICKI, reflecting altered insulin sensitivity and lower GDI reflecting poorer beta-cell function. The presence of multiple risk factors for type 2 diabetes suggests that aggressive screening of the early adolescent FDR of women with PCOS is indicated.

  1. Sustained nonoxidative glucose utilization and depletion of glycogen in reperfused canine myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Schwaiger, M.; Neese, R.A.; Araujo, L.; Wyns, W.; Wisneski, J.A.; Sochor, H.; Swank, S.; Kulber, D.; Selin, C.; Phelps, M.

    1989-03-01

    Ischemically injured reperfused myocardium is characterized by increased 18F-fluorodeoxyglucose uptake as demonstrated by positron emission tomography. To elucidate the metabolic fate of exogenous glucose entering reperfused myocardium, D-(6-14C) glucose and L-(U-13C) lactate were used to determine glucose uptake, glucose oxidation and the contribution of exogenous glucose to lactate production. The pathologic model under investigation consisted of a 3 h balloon occlusion of the left anterior descending coronary artery followed by 24 h of reperfusion in canine myocardium. The extent and severity of myocardial injury after the ischemia and reperfusion were assessed by histochemical evaluation (triphenyltetrazolium chloride and periodic acid-Schiff stains). Thirteen intervention and four control dogs were studied. The glucose uptake in the occluded/reperfused area was significantly enhanced compared with that in control dogs (0.40 +/- 0.14 versus 0.15 +/- 0.10 mumol/ml, respectively). In addition, a significantly greater portion of the glucose extracted immediately entered glycolysis in the intervention group (75%) than in the control dogs (33%). The activity of the nonoxidative glycolytic pathway was markedly increased in the ischemically injured reperfused area, as evidenced by the four times greater lactate release in this area compared with the control value. The dual carbon-labeled isotopes showed that 57% of the exogenous glucose entering glycolysis was being converted to lactate. Exogenous glucose contributed to greater than 90% of the observed lactate production. This finding was confirmed by the histochemical finding of sustained glycogen depletion in the occlusion/reperfusion area. The average area of glycogen depletion (37%) significantly exceeded the average area of necrosis (17%).

  2. Association of urinary metal profiles with altered glucose levels and diabetes risk: a population-based study in China.

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    Wei Feng

    Full Text Available Elevated heavy metals and fasting plasma glucose (FPG levels were both associated with increased risk of cardiovascular diseases. However, studies on the associations of heavy metals and essential elements with altered FPG and diabetes risk were limited or conflicting. The objective of this study was to evaluate the potential associations of heavy metals and essential trace elements with FPG and diabetes risk among general Chinese population.We conducted a cross-sectional study to investigate the associations of urinary concentrations of 23 metals with FPG, impaired fasting glucose (IFG and diabetes among 2242 community-based Chinese adults in Wuhan. We used the false discovery rate (FDR method to correct for multiple hypothesis tests.After adjusting for potential confounders, urinary aluminum, titanium, cobalt, nickel, copper, zinc, selenium, rubidium, strontium, molybdenum, cadmium, antimony, barium, tungsten and lead were associated with altered FPG, IFG or diabetes risk (all P< 0.05; arsenic was only dose-dependently related to diabetes (P< 0.05. After additional adjustment for multiple testing, titanium, copper, zinc, selenium, rubidium, tungsten and lead were still significantly associated with one or more outcomes (all FDR-adjusted P< 0.05.Our results suggest that multiple metals in urine are associated with FPG, IFG or diabetes risk. Because the cross-sectional design precludes inferences about causality, further prospective studies are warranted to validate our findings.

  3. The effect of insulin resistance on amygdale glucose metabolism alterations in experimental Alzheimer’s disease

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    Ya. V. Gorina

    2017-01-01

    Full Text Available Purpose. Glucose metabolism is tightly regulated in the brain. Aberrant glucose metabolism is an important feature of neurodegenerative diseases, as inAlzheimer’s disease. The transport of glucose to the cell membrane is realized through the activity of insulin-regulated aminopeptidase (IRAP which controls transfer of glucose transporter to the plasma membrane. IRAP is considered as one of the key markers of insulin resistance in Alzheimer’s disease. However, the question of the mechanism of the action of the IRAP remains open. The aim of the study was to study the effect of IRAP expression on cells of the neuronal and glial lineage, glucose transporter (GLUT4 expression in the brain amygdala on emotional memory in animals with experimental Alzheimer’s disease.Materials and methods. The study was performed with two experimental models of Alzheimer’s disease in mice. The experimental group was mice of the CD1 line, males aged 4 months (Alzheimer’s disease model with the intra-hippocampal administration of beta-amyloid 1-42 (1 µl bilaterally in the CA1 area. The control group was mice of the CD1 line, males aged 4 months (sham-operated animals with the intrahippocampal administration of Phosphate buffered salin (1 µl bilaterally in the CA1. The genetic model of Alzheimer’s disease is the B6SLJ-Tg line mice (APPSwFlLon, PSEN1*M146L*L286V 6799Vas, males aged 4 months. The control group consisted of C57BL/6xSJL mice, males aged 4 months. Evaluation of emotional memory was carried out using “Fear conditioning” protocol. Expression of molecule-markers of insulin-resistance in the amygdala was studied by immunohistochemistry followed by confocal microscopy.Results. Aberrant associative learning and emotional memory was revealed in animals with an experimental model of Alzheimer’s disease. A decrease (p ≤ 0,05 of IRAP expression on cells of neuronal and glial nature, associated with GLUT4 down-regulation was detected in amygdala of

  4. 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

  5. Maltose and maltodextrin utilization by Listeria monocytogenes depend on an inducible ABC transporter which is repressed by glucose.

    Directory of Open Access Journals (Sweden)

    Shubha Gopal

    2010-04-01

    Full Text Available In the environment as well as in the vertebrate intestine, Listeriae have access to complex carbohydrates like maltodextrins. Bacterial exploitation of such compounds requires specific uptake and utilization systems.We could show that Listeria monocytogenes and other Listeria species contain genes/gene products with high homology to the maltodextrin ABC transporter and utilization system of B. subtilis. Mutant construction and growth tests revealed that the L. monocytogenes gene cluster was required for the efficient utilization of maltodextrins as well as maltose. The gene for the ATP binding protein of the transporter was located distant from the cluster. Transcription analyses demonstrated that the system was induced by maltose/maltodextrins and repressed by glucose. Its induction was dependent on a LacI type transcriptional regulator. Repression by glucose was independent of the catabolite control protein CcpA, but was relieved in a mutant defective for Hpr kinase/phosphorylase.The data obtained show that in L. monocytogenes the uptake of maltodextrin and, in contrast to B. subtilis, also maltose is exclusively mediated by an ABC transporter. Furthermore, the results suggest that glucose repression of the uptake system possibly is by inducer exclusion, a mechanism not described so far in this organism.

  6. Glucose concentration and streptomycin alter in vitro muscle function and metabolism.

    Science.gov (United States)

    Khodabukus, Alastair; Baar, Keith

    2015-06-01

    Cell culture conditions can vary between laboratories and have been optimised for 2D cell culture. In this study, engineered muscle was cultured in 5.5 mM low glucose (LG) or 25 mM high glucose (HG) and in the absence or presence (+S) of streptomycin and the effect on C2C12 tissue-engineered muscle function and metabolism was determined. Following 2 weeks differentiation, streptomycin (3-fold) and LG (0.5-fold) significantly decreased force generation. LG and/or streptomycin resulted in upward and leftward shifts in the force-frequency curve and slowed time-to-peak tension and half-relaxation time. Despite changes in contractile dynamics, no change in myosin isoform was detected. Instead, changes in troponin isoform, calcium sequestering proteins (CSQ and parvalbumin) and the calcium uptake protein SERCA predicted the changes in contractile dynamics. Culturing in LG and/or streptomycin resulted in increased fatigue resistance despite no change in the mitochondrial enzymes SDH, ATPsynthase and cytochrome C. However, LG resulted in increases in the β-oxidation enzymes LCAD and VLCAD and the fatty acid transporter CPT-1, indicative of a greater capacity for fat oxidation. In contrast, HG resulted in increased GLUT4 content and the glycolytic enzyme PFK, indicative of a more glycolytic phenotype. These data suggest that streptomycin has negative effects on force generation and that glucose can be used to shift engineered muscle phenotype via changes in calcium-handling and metabolic proteins. © 2014 Wiley Periodicals, Inc.

  7. Development of a glucose sensor employing quick and easy modification method with mediator for altering electron acceptor preference.

    Science.gov (United States)

    Hatada, Mika; Loew, Noya; Inose-Takahashi, Yuka; Okuda-Shimazaki, Junko; Tsugawa, Wakako; Mulchandani, Ashok; Sode, Koji

    2018-02-09

    Enzyme based electrochemical biosensors are divided into three generations according to their type of electron transfer from the cofactors of the enzymes to the electrodes. Although the 3rd generation sensors using direct electron transfer (DET) type enzymes are ideal, the number of enzyme types which possess DET ability is limited. In this study, we report of a glucose sensor using mediator-modified glucose dehydrogenase (GDH), that was fabricated by a new quick-and-easy method using the pre-functionalized amine reactive phenazine ethosulfate (arPES). Thus mediator-modified GDH obtained the ability to transfer electrons to bulky electron acceptors as well as electrodes. The concentration of glucose was successfully measured using electrodes with immobilized PES-modified GDH, without addition of external electron mediators. Therefore, continuous monitoring systems can be developed based on this "2.5th generation" electron transfer principle utilizing quasi-DET. Furthermore, we successfully modified two other diagnostically relevant enzymes, glucoside 3-dehydrogenase and lactate oxidase, with PES. Therefore, various kinds of diagnostic enzymes can achieve quasi-DET ability simply by modification with arPES, suggesting that continuous monitoring systems based on the 2.5th generation principle can be developed for various target molecules. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Diglycosyl diselenides alter redox homeostasis and glucose consumption of infective African trypanosomes

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    Jaime Franco

    2017-12-01

    Full Text Available With the aim to develop compounds able to target multiple metabolic pathways and, thus, to lower the chances of drug resistance, we investigated the anti-trypanosomal activity and selectivity of a series of symmetric diglycosyl diselenides and disulfides. Of 18 compounds tested the fully acetylated forms of di-β-D-glucopyranosyl and di-β-D-galactopyranosyl diselenides (13 and 15, respectively displayed strong growth inhibition against the bloodstream stage of African trypanosomes (EC50 0.54 μM for 13 and 1.49 μM for 15 although with rather low selectivity (SI < 10 assayed with murine macrophages. Nonacetylated versions of the same sugar diselenides proved to be, however, much less efficient or completely inactive to suppress trypanosome growth. Significantly, the galactosyl (15, and to a minor extent the glucosyl (13, derivative inhibited glucose catabolism but not its uptake. Both compounds induced redox unbalance in the pathogen. In vitro NMR analysis indicated that diglycosyl diselenides react with glutathione, under physiological conditions, via formation of selenenylsulfide bonds. Our results suggest that non-specific cellular targets as well as actors of the glucose and the redox metabolism of the parasite may be affected. These molecules are therefore promising leads for the development of novel multitarget antitrypanosomal agents. Keywords: Glutathione, Redox biosensor, Selenosugar, Trypanosome inhibition, Selenium NMR

  9. Effect of feeding garlic leaves on rumen fermentation, methane emission, plasma glucose kinetics, and nitrogen utilization in sheep

    Directory of Open Access Journals (Sweden)

    Arvinda Panthee

    2017-06-01

    Full Text Available Abstract Background Garlic and its constituents are reported to have been effective in reducing methane emission and also influence glucose metabolism in body; however, studies in ruminants using garlic leaves are scarce. Garlic leaves contain similar compounds as garlic bulbs, but are discarded in field after garlic bulb harvest. We speculate that feeding garlic leaves might show similar effect as garlic constituents in sheep and could be potential animal feed supplement. Thus, we examined the effect of freeze dried garlic leaves (FDGL on rumen fermentation, methane emission, plasma glucose kinetics and nitrogen utilization in sheep. Methods Six sheep were fed Control diet (mixed hay and concentrate (60:40 or FDGL diet (Control diet supplemented with FDGL at 2.5 g/kg BW0.75 of sheep using a crossover design. Methane gas emission was measured using open-circuit respiratory chamber. Plasma glucose turnover rate was measured using isotope dilution technique of [U-13C]glucose. Rumen fluid, feces and urine were collected to measure rumen fermentation characteristics and nitrogen utilization. Result No significant difference in rumen fermentation parameters was noticed except for rumen ammonia tended to be higher (0.05 < P < 0.1 in FDGL diet. Methane emission per kg dry matter ingested and methane emission per kg dry matter digested were lower (P < 0.05 in FDGL diet. Plasma glucose concentration was similar between diets and plasma glucose turnover rate tended to be higher in FDGL diet (0.05 < P < 0.1. Nitrogen retention was higher (P < 0.05 and microbial nitrogen supply tended to be higher (0.05 < P < 0.1 in FDGL diet. Conclusion FDGL diet did not impair rumen fermentation, improved nitrogen retention; while absence of significant results in reduction of methane emission, glucose turnover rate and microbial nitrogen supply, further studies at higher dose would be necessary to conclude the merit of FDGL as supplement in ruminant

  10. Increasing protein at the expense of carbohydrate in the diet down-regulates glucose utilization as glucose sparing effect in rats.

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    Magdalena Stepien

    Full Text Available High protein (HP diet could serve as a good strategy against obesity, provoking the changes in energy metabolic pathways. However, those modifications differ during a dietary adaptation. To better understand the mechanisms involved in effect of high protein diet (HP on limiting adiposity in rats we studied in parallel the gene expression of enzymes involved in protein and energy metabolism and the profiles of nutrients oxidation. Eighty male Wistar rats were fed a normal protein diet (NP, 14% of protein for one week, then either maintained on NP diet or assigned to a HP diet (50% of protein for 1, 3, 6 and 14 days. mRNA levels of genes involved in carbohydrate and lipid metabolism were measured in liver, adipose tissues, kidney and muscles by real time PCR. Energy expenditure (EE and substrate oxidation were measured by indirect calorimetry. Liver glycogen and plasma glucose and hormones were assayed. In liver, HP feeding 1 decreased mRNA encoding glycolysis enzymes (GK, L-PK and lipogenesis enzymes(ACC, FAS, 2 increased mRNA encoding gluconeogenesis enzymes (PEPCK, 3 first lowered, then restored mRNA encoding glycogen synthesis enzyme (GS, 4 did not change mRNA encoding β-oxidation enzymes (CPT1, ACOX1, βHAD. Few changes were seen in other organs. In parallel, indirect calorimetry confirmed that following HP feeding, glucose oxidation was reduced and fat oxidation was stable, except during the 1(st day of adaptation where lipid oxidation was increased. Finally, this study showed that plasma insulin was lowered and hepatic glucose uptake was decreased. Taken together, these results demonstrate that following HP feeding, CHO utilization was increased above the increase in carbohydrate intake while lipogenesis was decreased thus giving a potential explanation for the fat lowering effect of HP diets.

  11. 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.

  12. Enzyme-free monitoring of glucose utilization in stimulated macrophages using carbon nanotube-decorated electrochemical sensor

    Science.gov (United States)

    Madhurantakam, Sasya; Karnam, Jayanth Babu; Rayappan, John Bosco Balaguru; Krishnan, Uma Maheswari

    2017-11-01

    Carbon nanotubes (CNTs) have been extensively explored for a diverse range of applications due to their unique electrical and mechanical properties. CNT-incorporated electrochemical sensors have exhibited enhanced sensitivity towards the analyte molecule due to the excellent electron transfer properties of CNTs. In addition, CNTs possess a large surface area-to-volume ratio that favours the adhesion of analyte molecules as well as enhances the electroactive area. Most of the electrochemical sensors have employed CNTs as a nano-interface to promote electron transfer and as an immobilization matrix for enzymes. The present work explores the potential of CNTs to serve as a catalytic interface for the enzymeless quantification of glucose. The figure of merits for the enzymeless sensor was comparable to the performance of several enzyme-based sensors reported in literature. The developed sensor was successfully employed to determine the glucose utilization of unstimulated and stimulated macrophages. The significant difference in the glucose utilization levels in activated macrophages and quiescent cells observed in the present investigation opens up the possibilities of new avenues for effective medical diagnosis of inflammatory disorders.

  13. Altered brain activity in women recovered from bulimic-type eating disorders after a glucose challenge: a pilot study.

    Science.gov (United States)

    Frank, Guido K; Wagner, Angela; Achenbach, Sarah; McConaha, Claire; Skovira, Kellie; Aizenstein, Howard; Carter, Cameron S; Kaye, Walter H

    2006-01-01

    It is not known whether individuals with bulimic-type eating disorders have a dysregulation of brain pathways that modulate appetite. Taste plays a role in the regulation of appetite and the purpose of the current study was to determine whether bulimic women have alterations in the physiologic response to the blind administration of glucose. To avoid the confounding effects of a current eating disorder, and to assess possibly trait-related disturbances, we studied 10 subjects recovered (> or = 1 year) from a bulimic-type eating disorder and 6 control women. Subjects were administered a solution of glucose or artificial saliva (control solution) in alternating blocks during a functional magnet resonance imaging scan. Individuals who recovered from a bulimic-type eating disorder had significantly lower activation in the right anterior cingulate cortex (ACC; Montreal Neurological Institute [MNI] coordinates x = 8, y = 22, z = 28; cluster size = 18 voxels, T = 5.11, Z-score = 3.78) and in the left cuneus (occipital cortex; MNI coordinates x = -12, y = -78, z = 10; cluster size = 21 voxels, T = 4.27, Z-score = 3.36), when glucose was compared with artificial saliva. The ACC plays a role in the anticipation of reward. Individuals with bulimic-type eating disorders may have a reduced reward response to nutrients, and thus may be vulnerable to overeating. However, this is a small sample and the current study will need replication in a larger sample size with investigation of additional regions of interest. 2005 by Wiley Periodicals, Inc.

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

    International Nuclear Information System (INIS)

    Dienel, G.A.; Nelson, T.; Cruz, N.F.; Jay, T.; Crane, A.M.; Sokoloff, L.

    1988-01-01

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

  15. The PPARα/γ Agonist, Tesaglitazar, Improves Insulin Mediated Switching of Tissue Glucose and Free Fatty Acid Utilization In Vivo in the Obese Zucker Rat

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    Kristina Wallenius

    2013-01-01

    Full Text Available Metabolic flexibility was assessed in male Zucker rats: lean controls, obese controls, and obese rats treated with the dual peroxisome proliferator activated receptor (PPAR agonist, tesaglitazar, 3 μmol/kg/day for 3 weeks. Whole body glucose disposal rate ( and hepatic glucose output (HGO were assessed under basal fasting and hyperinsulinemic isoglycemic clamp conditions using [3,3H]glucose. Indices of tissue specific glucose utilization ( were measured at basal, physiological, and supraphysiological levels of insulinemia using 2-deoxy-D-[2,6-3H]glucose. Finally, whole body and tissue specific FFA and glucose utilization and metabolic fate were evaluated under basal and hyperinsulinemic conditions using a combination of [U-13C]glucose, 2-deoxy-D-[U-14C]glucose, [U-14C]palmitate, and [9,10-3H]-(R-bromopalmitate. Tesaglitazar improved whole body insulin action by greater suppression of HGO and stimulation of compared to obese controls. This involved increased insulin stimulation of in fat and skeletal muscle as well as increased glycogen synthesis. Tesaglitazar dramatically improved insulin mediated suppression of plasma FFA level, whole body turnover (, and muscle, liver, and fat utilization. At basal insulin levels, tesaglitazar failed to lower HGO or compared to obese controls. In conclusion, the results demonstrate that tesaglitazar has a remarkable ability to improve insulin mediated control of glucose and FFA fluxes in obese Zucker rats.

  16. Microarray Analysis Reveals Altered Lipid and Glucose Metabolism Genes in Differentiated, Ritonavir-Treated 3T3-L1 Adipocytes.

    Science.gov (United States)

    Loonam, Cathriona R; O'Dell, Sandra D; Sharp, Paul A; Mullen, Anne

    2016-01-01

    HIV lipodystrophy is characterised by abnormal adipose tissue distribution and metabolism, as a result of altered adipocyte function and gene expression. The protease inhibitor ritonavir is associated with the development of lipodystrophy. Quantifying changes in adipogenic gene expression in the presence of ritonavir may help to identify therapeutic targets for HIV lipodystrophy. Affymetrix Mouse Genome 430 2.0 oligonucleotide microarray was used to investigate gene expression in 3T3-L1 adipocytes treated with 20 µmol/l ritonavir or vehicle control (ethanol). Pparg, Adipoq, Retn and Il6 expression were validated by real time RT-PCR. Transcriptional signalling through PPAR-γ was investigated using a DNA-binding ELISA. Changes in adipocyte function were investigated through secreted adiponectin quantification using ELISA and Oil Red O staining for triglyceride storage. Expression of 389 genes was altered by more than 5-fold in the presence of ritonavir (all P Gene ontology analysis revealed down-regulation of genes responsible for adipocyte triglyceride accumulation including complement factor D (Cfd; 238.42-fold), Cidec (73.75-fold) and Pparg (5.63-fold). Glucose transport genes were also down-regulated including Adipoq (24.42-fold) and Glut4 (13.36-fold), while Il6 was up-regulated (10.39-fold). PPAR-γ regulatory genes Cebpa (11.33-fold) and liver-X-receptor α (Nr1h3) were down-regulated. Changes in Pparg, Adipoq and Il6 were confirmed by RT-PCR. PPAR-γ binding to its nuclear consensus site, adiponectin secretion and triglyceride accumulation were all reduced by ritonavir. Ritonavir had a significant effect on expression of genes involved in adipocyte differentiation, lipid accumulation and glucose metabolism. Down-regulation of Pparg may be mediated by changes in Cebpa, Lcn2 and Nr1h3.

  17. The prevalence of impaired glucose regulation in psychiatric patients with sleep disorders and its relationship with altered hypothalamopituitary-adrenal and hypothalamopituitary-thyroid axis activity.

    Science.gov (United States)

    Li, Jiaqi; Sun, Xueli; Yu, Yerong

    2013-07-01

    Sleep restriction, an important symptom of psychiatric diseases, is associated with adverse effects on glucose regulation, but few studies have examined its association with impaired glucose regulation and altered hypothalamic activity. Our study was designed to evaluate the sleep duration, fasting glucose, tolerance glucose, and concentration of plasma insulin; to assess the function of both the hypothalamopituitary-thyroid (HPT) and hypothalamopituitary-adrenal (HPA) axis; and to investigate the relationship of altered hypothalamic function with glucose metabolism in psychiatric patients with a sleep disorders. From January 2010 to December 2011, 324 women (64.7%) and 177 men (35.32%) with a diagnosis of a sleep disorder participated in our cross-sectional study in the psychiatric outpatient department of the West China Hospital of Sichuan University. Results from 75-g glucose tolerance tests, insulin-releasing tests, morning (8:00 am) serum cortisol, and thyroid-stimulating hormone (TSH) (TT3, TT4, FT3, FT4) were collected, as well as body mass index and waist-hip ratio to assess the prevalence of impaired glucose regulation and function of the HPA and HPT axis. Sleep quality was assessed through self-reported questionnaires. There were 301 patients previously diagnosed with an anxiety disorder (78%), and 200 patients previously diagnosed with depression and other psychiatric diseases (22%). Crude prevalence rates were 15.0% for diabetes mellitus (DM), 11.6% for impaired glucose tolerance, 15.8% for impaired fasting glucose, and 11.6% for impaired glucose regulation (impaired glucose tolerance [IGT]+impaired fasting glucose [IFG]). Total prevalence of impaired glucose regulation in patients with a sleep disorder was 48.8%. Mean cortisol level was 463.5±178.8 nmol/L, and the cortisol concentration at 8:00 am was significantly associated with a higher prevalence of impaired glucose regulation and insulin resistance. TSH values above 2.5 mU/L accounted for over 58

  18. Alteration of endothelial proteoglycan and heparanase gene expression by high glucose, insulin and heparin.

    Science.gov (United States)

    Han, J; Hiebert, L M

    2013-01-01

    Heparan sulfate proteoglycans (HSPGs) contain a core protein with glycosaminoglycans attached. Reduced glycosaminoglycan, in endothelial HSPGs syndecan and perlecan, is associated with diabetic cardiovascular complications but changes in core protein remain controversial. Since heparanase degrades heparan sulfate, we wished to determine if changes in endothelial heparanase mRNA, by high glucose (HG), correlate with changes in syndecan and perlecan core proteins, and to observe effects of heparin or insulin. RNA was isolated from cultured human aortic endothelial cells treated with HG (30mM), insulin (0.01 units/mL), heparin (0.5μg/mL), HG plus heparin and/or insulin for 24h. Real time PCR revealed that HG alone significantly increased heparanase, decreased syndecan with no effect on perlecan mRNA. Heparin or insulin significantly prevented the increase in heparanase but decreased perlecan mRNA while heparin, but not insulin, prevented the decrease in syndecan mRNA in HG treated cells. HG plus heparin and insulin increased heparanase and syndecan mRNA compared to all other treatments and decreased perlecan mRNA compared to control and HG alone. Heparin may protect endothelium from HG injury by reducing heparanase and increasing syndecan while insulin inhibits heparanase expression. Effects with insulin plus heparin suggest interference in transcriptional regulation of heparanase and syndecan genes. © 2013.

  19. Suppression of glucose-6-phosphate-isomerase induced arthritis by oral administration of transgenic rice seeds expressing altered peptide ligands of glucose-6-phosphate-isomerase.

    Science.gov (United States)

    Hirota, Tomoya; Tsuboi, Hiroto; Iizuka-Koga, Mana; Takahashi, Hiroyuki; Asashima, Hiromitsu; Yokosawa, Masahiro; Kondo, Yuya; Ohta, Masaru; Wakasa, Yuhya; Matsumoto, Isao; Takaiwa, Fumio; Sumida, Takayuki

    2017-05-01

    To investigate the effects of transgenic rice seeds expressing the altered peptide ligand (APL) of human glucose-6-phosphate-isomerase (hGPI 325-339 ) in mice model of GPI-induced arthritis (GIA). We generated transgenic rice expressing T-cell epitope of hGPI 325-339 and APL12 contained in the seed endosperm. The transgenic rice seeds were orally administered prophylactically before the induction of GIA. The severity of arthritis and titers of serum anti-GPI antibodies were evaluated. We examined for IL-17 production in splenocytes and inguinal lymph node (iLN) cells, and analyzed the expression levels of functional molecules in splenocytes. Prophylactic treatment of GIA mice with APL12 transgenic (APL12-TG) rice seeds significantly reduced the severity of arthritis and titers of serum anti-GPI antibodies compared with non-transgenic (Non-TG) rice-treated mice. APL12-TG and hGPI 325-339 transgenic (hGPI 325-339 -TG) rice seeds improved the histopathological arthritis scores and decreased IL-17 production compared with non-TG rice-treated mice. APL12-TG rice-treated GIA mice showed upregulation of Foxp3 and GITR protein in CD4  +  CD25  +  Foxp3 +  cells in the spleen compared with non-TG rice- and hGPI 325-339 -TG rice-treated mice. APL12-TG rice seeds improved the severity of GIA through a decrease in production of IL-17 and anti-GPI antibodies via upregulation of Foxp3 and GITR expression on Treg cells in spleen.

  20. The clinical utility of two human portable blood glucose meters in canine and feline practice.

    Science.gov (United States)

    Domori, Asuka; Sunahara, Ayano; Tateno, Morihiro; Miyama, Takako Shimokawa; Setoguchi, Asuka; Endo, Yasuyuki

    2014-03-01

    Portable blood glucose meters (PBGMs) are useful for serial measurements of blood glucose and creation of blood glucose curves in veterinary practice. However, it is necessary to validate PBGMs designed for people for veterinary use. Our objective was to evaluate the accuracy of 2 PBGMs designed for people for use in dogs and cats. The blood glucose levels were determined in blood samples collected from 69 dogs and 26 cats admitted to the Kagoshima University Veterinary Teaching Hospital, using a MEDISAFE [PBGM-T] and an Antsense III [PBGM-H], and a FUJI DRI-CHEM 7000V as reference method. The correlations and agreements among the results were statistically analyzed. Simple regression analyses revealed a high correlation between values from both PBGMs and the reference method in both dogs and cats. However, Passing-Bablok regression and Bland-Altman analyses revealed that the data from both PBGMs did not show statistical agreement with the reference values. Concordance correlated coefficients were moderate for the PBGM-T and almost perfect for the PBGM-H for canine samples, and were poor for the PBGM-T and substantial for the PBGM-H for feline samples. Hematocrit values significantly affected the results of the PBGM-T, but not the PBGM-H. Error grid analyses revealed that all measurements from both PBGMs would lead to acceptable treatment decisions. Our findings suggest that both PBGMs, especially the PBGM-H, would be clinically useful in small animal practice, although there was a bias between each PBGM and the reference method. © 2014 American Society for Veterinary Clinical Pathology and European Society for Veterinary Clinical Pathology.

  1. Mobilization and removing of cadmium from kidney by GMDTC utilizing renal glucose reabsorption pathway.

    Science.gov (United States)

    Tang, Xiaojiang; Zhu, Jinqiu; Zhong, Zhiyong; Luo, Minhui; Li, Guangxian; Gong, Zhihong; Zhang, Chenzi; Fei, Fan; Ruan, Xiaolin; Zhou, Jinlin; Liu, Gaofeng; Li, Guoding; Olson, James; Ren, Xuefeng

    2016-08-15

    Chronic exposure to cadmium compounds (Cd(2+)) is one of the major public health problems facing humans in the 21st century. Cd(2+) in the human body accumulates primarily in the kidneys which leads to renal dysfunction and other adverse health effects. Efforts to find a safe and effective drug for removing Cd(2+) from the kidneys have largely failed. We developed and synthesized a new chemical, sodium (S)-2-(dithiocarboxylato((2S,3R,4R,5R)-2,3,4,5,6 pentahydroxyhexyl)amino)-4-(methylthio) butanoate (GMDTC). Here we report that GMDTC has a very low toxicity with an acute lethal dose (LD50) of more than 10,000mg/kg or 5000mg/kg body weight, respectively, via oral or intraperitoneal injection in mice and rats. In in vivo settings, up to 94% of Cd(2+) deposited in the kidneys of Cd(2+)-laden rabbits was removed and excreted via urine following a safe dose of GMDTC treatment for four weeks, and renal Cd(2+) level was reduced from 12.9μg/g to 1.3μg/g kidney weight. We observed similar results in the mouse and rat studies. Further, we demonstrated both in in vitro and in animal studies that the mechanism of transporting GMDTC and GMDTC-Cd complex into and out of renal tubular cells is likely assisted by two glucose transporters, sodium glucose cotransporter 2 (SGLT2) and glucose transporter 2 (GLUT2). Collectively, our study reports that GMDTC is safe and highly efficient in removing deposited Cd(2+) from kidneys assisted by renal glucose reabsorption system, suggesting that GMDTC may be the long-pursued agent used for preventive and therapeutic purposes for both acute and chronic Cd(2+) exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Utilizing microfluidics to synthesize polyethylene glycol microbeads for Förster resonance energy transfer based glucose sensing

    Science.gov (United States)

    Kantak, Chaitanya; Zhu, Qingdi; Beyer, Sebastian; Bansal, Tushar; Trau, Dieter

    2012-01-01

    Here, we utilize microfluidic droplet technology to generate photopolymerizeable polyethylene glycol (PEG) hydrogel microbeads incorporating a fluorescence-based glucose bioassay. A microfluidic T-junction and multiphase flow of fluorescein isothiocyanate dextran, tetramethyl rhodamine isothiocyanate concanavalin A, and PEG in water were used to generate microdroplets in a continuous stream of hexadecane. The microdroplets were photopolymerized mid-stream with ultraviolet light exposure to form PEG microbeads and were collected at the outlet for further analysis. Devices were prototyped in PDMS and generated highly monodisperse 72 ± 2 μm sized microbeads (measured after transfer into aqueous phase) at a continuous flow rate between 0.04 ml/h—0.06 ml/h. Scanning electron microscopy analysis was conducted to analyze and confirm microbead integrity and surface morphology. Glucose sensing was carried out using a Förster resonance energy transfer (FRET) based assay. A proportional fluorescence intensity increase was measured within a 1–10 mM glucose concentration range. Microfluidically synthesized microbeads encapsulating sensing biomolecules offer a quick and low cost method to generate monodisperse biosensors for a variety of applications including cell cultures systems, tissue engineering, etc. PMID:22655010

  3. Quantitative metabolomics of a xylose-utilizing Saccharomyces cerevisiae strain expressing the Bacteroides thetaiotaomicron xylose isomerase on glucose and xylose.

    Science.gov (United States)

    Mert, M J; Rose, S H; la Grange, D C; Bamba, T; Hasunuma, T; Kondo, A; van Zyl, W H

    2017-10-01

    The yeast Saccharomyces cerevisiae cannot utilize xylose, but the introduction of a xylose isomerase that functions well in yeast will help overcome the limitations of the fungal oxido-reductive pathway. In this study, a diploid S. cerevisiae S288c[2n YMX12] strain was constructed expressing the Bacteroides thetaiotaomicron xylA (XI) and the Scheffersomyces stipitis xyl3 (XK) and the changes in the metabolite pools monitored over time. Cultivation on xylose generally resulted in gradual changes in metabolite pool size over time, whereas more dramatic fluctuations were observed with cultivation on glucose due to the diauxic growth pattern. The low G6P and F1,6P levels observed with cultivation on xylose resulted in the incomplete activation of the Crabtree effect, whereas the high PEP levels is indicative of carbon starvation. The high UDP-D-glucose levels with cultivation on xylose indicated that the carbon was channeled toward biomass production. The adenylate and guanylate energy charges were tightly regulated by the cultures, while the catabolic and anabolic reduction charges fluctuated between metabolic states. This study helped elucidate the metabolite distribution that takes place under Crabtree-positive and Crabtree-negative conditions when cultivating S. cerevisiae on glucose and xylose, respectively.

  4. 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.

  5. Decreased labeling of amino acids by inhibition of the utilization of [3H, 14C]glucose via the hexosemonophosphate shunt in rat brain in vivo

    International Nuclear Information System (INIS)

    Gaitonde, M.K.; James, M.D.; Evans, G.M.

    1984-01-01

    Treatment of rats with 6-aminonicotinamide showed a small but significant decrease in the labeling of amino acids in the brain after injection of [ 3 H]acetate. The results of these experiments also gave evidence of the presence of [ 3 H]glucose and [ 3 H]acetate, and an increase in [ 3 H]glucose content in the brain of 6-aminonicotinamide treated rats. To apportion the contribution of [ 3 H]glucose formed by gluconeogenesis from [ 3 H]acetate to the labeling of amino acids a method was formulated based on the measurement of radioactivity of amino acids, lactate and free sugars in brain after injection of [6- 3 H]glucose or [1- 3 H]glucose relative to that after co-injection of [U- 14 C]glucose or [2- 14 C]glucose. These findings indicated that a significant decrease in the labeling of amino acids from [U-14C]glucose reported previously and again confirmed using [1- 3 H], [6- 3 H], [2- 14 C] or [U- 14 C]glucose in the present investigation was not due to the inhibition of the activities of enzymes of the citric acid cycle. These results support the postulated role of the hexosemonophosphate shunt for the utilization of glucose in providing neurotransmitter amino acids glutamate and gamma-aminobutyrate

  6. B-Cell-Specific Diversion of Glucose Carbon Utilization Reveals a Unique Vulnerability in B Cell Malignancies.

    Science.gov (United States)

    Xiao, Gang; Chan, Lai N; Klemm, Lars; Braas, Daniel; Chen, Zhengshan; Geng, Huimin; Zhang, Qiuyi Chen; Aghajanirefah, Ali; Cosgun, Kadriye Nehir; Sadras, Teresa; Lee, Jaewoong; Mirzapoiazova, Tamara; Salgia, Ravi; Ernst, Thomas; Hochhaus, Andreas; Jumaa, Hassan; Jiang, Xiaoyan; Weinstock, David M; Graeber, Thomas G; Müschen, Markus

    2018-04-05

    B cell activation during normal immune responses and oncogenic transformation impose increased metabolic demands on B cells and their ability to retain redox homeostasis. While the serine/threonine-protein phosphatase 2A (PP2A) was identified as a tumor suppressor in multiple types of cancer, our genetic studies revealed an essential role of PP2A in B cell tumors. Thereby, PP2A redirects glucose carbon utilization from glycolysis to the pentose phosphate pathway (PPP) to salvage oxidative stress. This unique vulnerability reflects constitutively low PPP activity in B cells and transcriptional repression of G6PD and other key PPP enzymes by the B cell transcription factors PAX5 and IKZF1. Reflecting B-cell-specific transcriptional PPP-repression, glucose carbon utilization in B cells is heavily skewed in favor of glycolysis resulting in lack of PPP-dependent antioxidant protection. These findings reveal a gatekeeper function of the PPP in a broad range of B cell malignancies that can be efficiently targeted by small molecule inhibition of PP2A and G6PD. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Neuroscience of glucose homeostasis

    NARCIS (Netherlands)

    La Fleur, S E; Fliers, E; Kalsbeek, A

    2014-01-01

    Plasma glucose concentrations are homeostatically regulated and maintained within strict boundaries. Several mechanisms are in place to increase glucose output when glucose levels in the circulation drop as a result of glucose utilization, or to decrease glucose output and increase tissue glucose

  8. Salivary alterations in type 1 diabetes mellitus patients: Salivary glucose could be noninvasive tool for monitoring diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Syed Shahbaz

    2014-01-01

    Conclusion: There are definite changes in salivary composition with increased levels of salivary glucose, total protein and albumin in T1DM patients compared with healthy controls. Salivary glucose could be used for monitoring of DM.

  9. Comparison of cancer glucose utilization indexes by positron emission tomography using fluorine-18-fluoro-deoxyglucose

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikawa, Kyosan (Chiba Univ. (Japan). School of Medicine)

    1994-08-01

    Positron emission tomography (PET) using fluorine-18-fluorodeoxyglucose (FDG) has been used to diagnose various kinds of malignant tumors. Various indexes are calculated for evaluation of tumor glucose metabolism from FDG PET image. Some indexes need sequential multiple-time uptake data and arterial plasma FDG concentrations (dynamic study). But some indexes use only static image data to calculate. We calculated four kinds of indexes on each patient, and analyzed the correlation of each index with others. Previously untreated 35 patients (23 non-Hodgikin's lymphoma, 4 lung cancers, 2 epipharynx cancers and other 6 malignant tumors) were studied by FDG PET. In all patients, about 4 mCi (148 MBq) of FDG was injected intravenously in a fasting state, and a series of 2-min sequential scans was acquired for 60 min following injection. After sequential scans, 6-min scan was successively added for obtaining static image. The rate constants (k[sub 1]-k[sub 4]) calculated by non-linear least squares fitting routines, the slope of Patlak-Gjedde plot, differential absorption ratio (DAR) which represents tumor activity corrected by administrated dose per body weight, and tumor-to-normal soft-tissue contrast ratios (TCR) were calculated for each patient. The correlation of these indexes was analyzed statistically. Patlak-Gjedde plot seemed to be widely accepted for measuring tumor glucose metabolism, but it needs dynamic study data. DAR is a simple index easily calculated using static data. Our results showed that the slope of Patlak-Gjedde plot and DAR were closely correlated. It was suggested that the DAR could be used in place of Patlak-Gjedde plot. They also showed relatively well correlation with each other. Correlation between rate constant k[sub 3] and other indexes were from 0.67 to 0.43. It is acceptable result because rate constant K[sub 3] related the activity of hexokinase but other indexes may represent the overall glucose metabolism of the tumor tissue. (J.N.P.).

  10. Butyric acid production from lignocellulosic biomass hydrolysates by engineered Clostridium tyrobutyricum overexpressing xylose catabolism genes for glucose and xylose co-utilization.

    Science.gov (United States)

    Fu, Hongxin; Yang, Shang-Tian; Wang, Minqi; Wang, Jufang; Tang, I-Ching

    2017-06-01

    Clostridium tyrobutyricum can utilize glucose and xylose as carbon source for butyric acid production. However, xylose catabolism is inhibited by glucose, hampering butyric acid production from lignocellulosic biomass hydrolysates containing both glucose and xylose. In this study, an engineered strain of C. tyrobutyricum Ct-pTBA overexpressing heterologous xylose catabolism genes (xylT, xylA, and xylB) was investigated for co-utilizing glucose and xylose present in hydrolysates of plant biomass, including soybean hull, corn fiber, wheat straw, rice straw, and sugarcane bagasse. Compared to the wild-type strain, Ct-pTBA showed higher xylose utilization without significant glucose catabolite repression, achieving near 100% utilization of glucose and xylose present in lignocellulosic biomass hydrolysates in bioreactor at pH 6. About 42.6g/L butyrate at a productivity of 0.56g/L·h and yield of 0.36g/g was obtained in batch fermentation, demonstrating the potential of C. tyrobutyricum Ct-pTBA for butyric acid production from lignocellulosic biomass hydrolysates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Oxidative stress in mouse sperm impairs embryo development, fetal growth and alters adiposity and glucose regulation in female offspring.

    Directory of Open Access Journals (Sweden)

    Michelle Lane

    Full Text Available Paternal health cues are able to program the health of the next generation however the mechanism for this transmission is unknown. Reactive oxygen species (ROS are increased in many paternal pathologies, some of which program offspring health, and are known to induce DNA damage and alter the methylation pattern of chromatin. We therefore investigated whether a chemically induced increase of ROS in sperm impairs embryo, pregnancy and offspring health. Mouse sperm was exposed to 1500 µM of hydrogen peroxide (H2O2, which induced oxidative damage, however did not affect sperm motility or the ability to bind and fertilize an oocyte. Sperm treated with H2O2 delayed on-time development of subsequent embryos, decreased the ratio of inner cell mass cells (ICM in the resulting blastocyst and reduced implantation rates. Crown-rump length at day 18 of gestation was also reduced in offspring produced by H2O2 treated sperm. Female offspring from H2O2 treated sperm were smaller, became glucose intolerant and accumulated increased levels of adipose tissue compared to control female offspring. Interestingly male offspring phenotype was less severe with increases in fat depots only seen at 4 weeks of age, which was restored to that of control offspring later in life, demonstrating sex-specific impacts on offspring. This study implicates elevated sperm ROS concentrations, which are common to many paternal health pathologies, as a mediator of programming offspring for metabolic syndrome and obesity.

  12. Studies of gene expression and activity of hexokinase, phosphofructokinase and glycogen synthase in human skeletal muscle in states of altered insulin-stimulated glucose metabolism

    DEFF Research Database (Denmark)

    Vestergaard, H

    1999-01-01

    of the review is to discuss our present knowledge of the activities and gene expression of hexokinase II (HKII), phosphofructokinase (PFK) and glycogen synthase (GS) in human skeletal muscle in states of altered insulin-stimulated glucose metabolism. My own experimental studies have comprised patients...... been reported to increase the basal concentration of muscle GS mRNA in NIDDM patients to a level similar to that seen in control subjects although insulin-stimulated glucose disposal rates remain reduced in NIDDM patients. In the insulin resistant states examined so far, basal and insulin...

  13. Patterns of glucose lowering drugs utilization in Portugal and in the Netherlands. Trends over time.

    Science.gov (United States)

    Torre, Carla; Guerreiro, José; de Oliveira Martins, Sofia; Raposo, João Filipe; Martins, Ana Paula; Leufkens, Hubert

    2015-12-01

    To compare the temporal trends in the consumption patterns of glucose lowering drugs (GLD) between Portugal and the Netherlands from 2004 to 2013 and to examine possible reasons behind the cross-national variation found. All GLD (ATC pharmacological subgroup A10B) were selected for analysis. Consumption data were obtained for the 10-year period. Portuguese and Dutch drug estimates were obtained from nationwide databases. The consumption of GLD increased in Portugal from 52.9 defined daily dose per 1000 inhabitants per day (DHD) in 2004 to 70.0 DHD in 2013 and in the Netherlands from 44.9 DHD in 2004 to 50.7 DHD in 2013. In Portugal, the use of fixed-dose combinations, especially with dipeptidyl peptidase-4 inhibitors (DPP-4) increased remarkably and in 2013 represented almost a quarter of total GLD consumption. In the Netherlands, the use of combinations was residual. The consumption of GLD rose over the 10-year period in both countries. However, Portuguese overall consumption and costs of GLD were higher. The differentially rapid uptake of DPP-4 inhibitors in Portugal was the main driver of the cost difference. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  14. Effect of 8 hours oxygen breathing at 2 atmosphere on glucose utilization in the rat

    International Nuclear Information System (INIS)

    Torbati, D.

    1986-01-01

    The regional cerebral metabolic rate for glucose (rCMRg1) was previously measured by [ 1 $C] 2-deoxyglucose autoradiographic method in conscious rats exposed to 2 atmosphere absolute oxygen (ATA O 2 ) up to 4 hours, and during various pre-convulsive periods of brain oxygen toxicity at 3 and 5 ATA O 2 . The exposures at 2 ATA O 2 did not produce any visible signs of pulmonary or brain oxygen toxicity as judged by lack of changes in the respiratory pattern and normal behavior. However, 1 h exposure to 2 ATA O 2 produced significant increases in rCMRg1 in various neuroanatomical structures. These increases were diminished following 4 h exposure to 2 ATA O 2 . In the present study the exposure time for rCMRg1 measurement was extended to 8 h oxygen breathing at 2 ATA O 2 , when obvious signs of respiratory distress developed. The data demonstrate no changes in rCMRg1 of the 28 neuroanatomical structures examined during oxygen breathing and normoxia at 2 ATA as compared to air breathing rats at 1 ATA. Thus, the early increases in rCMRg1 at 2 ATA O 2 seem to be a transient physiological phenomenon. It is concluded that unlike exposures to 3 and 5 ATA O 2 , the respiratory system at 2 ATA O 2 in conscious rats is more sensitive to the toxic effects of oxygen than the central nervous system

  15. Novel molecular mechanisms of antitumor action of dichloroacetate against T cell lymphoma: Implication of altered glucose metabolism, pH homeostasis and cell survival regulation.

    Science.gov (United States)

    Kumar, Ajay; Kant, Shiva; Singh, Sukh Mahendra

    2012-07-30

    Pyruvate dehydrogenase kinase (PDK) inhibits pyruvate dehydrogenase (PDH) activity and thus promotes energetic switch from mitochondrial glucose oxidation to cytoplasmic glycolysis in cancerous cells (a phenomenon known as the 'Warburg effect') for their energy need, which facilitates the cancer progression by resisting induction of apoptosis and promoting tumor metastasis. Thus, in the present investigation, we explored the molecular mechanisms of the tumoricidal action of dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor, on cells of a murine T cell lymphoma, designated as Dalton's lymphoma (DL). In vitro treatment of tumor cells with DCA inhibited their survival accompanied by a modulation of the biophysical composition of tumor-conditioned medium with respect to pH, glucose and lactate. DCA treatment also altered expression of HIF1-α and pH regulators: VATPase and MCT1 and production of cytokines: IL-10, IL-6 and IFN-γ. Moreover, we also observed an alteration in the expression of other apoptosis and cell survival regulatory molecules: PUMA, GLUT1, Bcl2, p53, CAD, caspase-3 and HSP70. The study discusses the role of novel molecular mechanisms underlying DCA-dependent inhibition of tumor cell survival. This study shows for the first time that DCA-dependent alteration of tumor cell survival involves altered pH homeostasis and glucose metabolism. Thus, these findings will provide a new insight for therapeutic applications of DCA as a novel antineoplastic agent against T cell lymphoma. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. Acute mTOR inhibition induces insulin resistance and alters substrate utilization in vivo

    DEFF Research Database (Denmark)

    Kleinert, Maximilian; Sylow, Lykke; Fazakerley, Daniel J

    2014-01-01

    The effect of acute inhibition of both mTORC1 and mTORC2 on metabolism is unknown. A single injection of the mTOR kinase inhibitor, AZD8055, induced a transient, yet marked increase in fat oxidation and insulin resistance in mice, whereas the mTORC1 inhibitor rapamycin had no effect. AZD8055...... SIN1 rescued glycolysis. Glucose intolerance following AZD8055 administration was absent in mice lacking the mTORC2 subunit Rictor in muscle, and in vivo glucose uptake into Rictor-deficient muscle was reduced despite normal Akt activity. Taken together, acute mTOR inhibition is detrimental to glucose...

  17. Acute mTOR inhibition induces insulin resistance and alters substrate utilization in vivo

    DEFF Research Database (Denmark)

    Kleinert, Maximilian; Sylow, Lykke; Fazakerley, Daniel J.

    2014-01-01

    The effect of acute inhibition of both mTORC1 and mTORC2 on metabolism is unknown. A single injection of the mTOR kinase inhibitor, AZD8055, induced a transient, yet marked increase in fat oxidation and insulin resistance in mice, whereas the mTORC1 inhibitor rapamycin had no effect. AZD8055...... SIN1 rescued glycolysis. Glucose intolerance following AZD8055 administration was absent in mice lacking the mTORC2 subunit Rictor in muscle, and in vivo glucose uptake into Rictor-deficient muscle was reduced despite normal Akt activity. Taken together, acute mTOR inhibition is detrimental to glucose...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-07-01

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

  19. Utility of hesperidinase for food function research: enzymatic digestion of botanical extracts alters cellular antioxidant capacities and anti-inflammatory properties.

    Science.gov (United States)

    Yu, Lu; Huang, Haiqiu; Yu, Liangli Lucy; Wang, Thomas T Y

    2014-08-27

    Food-derived phytochemicals, many known for their health beneficial effects, often exist in conjugated forms containing sugar moieties such as glucose or rhamnose in foods. The uptake of these compounds requires colonic bacterial cleavage of sugar moieties. However, most studies involved in screening extracts for biological activities do not take this process into account. This study seeks to determine the utility of commercially available hesperidinase to mimic colonic digestion and to test the effects of this treatment on the biological properties of extracts. Using hesperidinase resulted in efficient hydrolysis of Engelhardia roxburghiana Wall. extract containing rhamnose conjugates. Enzymatic digestion enhanced the extract's cellular antioxidant ability by 2-fold in HepG2/C3A and the anti-inflammatory effect on lipopolysaccharide-induced interleukin (IL)-1β and IL-6 expression in mouse macrophage J774A.1 and human monocyte THP-1 cells. Enzymatic digestion also efficiently processed extracts with mixed rhamnose and glucose conjugates and altered their biological activities. Results of the present study supported the importance of considering enzymatic digestion during the biological activity studies of botanicals.

  20. Alterations in blood glucose and plasma glucagon concentrations during deep brain stimulation in the shell region of the nucleus accumbens in rats

    Directory of Open Access Journals (Sweden)

    Charlene eDiepenbroek

    2013-12-01

    Full Text Available Deep brain stimulation (DBS of the nucleus accumbens (NAc is an effective therapy for obsessive compulsive disorder (OCD and is currently under investigation as a treatment for eating disorders. DBS of this area is associated with altered food intake and pharmacological treatment of OCD is associated with the risk of developing type 2 diabetes. Therefore we examined if DBS of the NAc-shell (sNAc influences glucose metabolism. Male Wistar rats were subjected to DBS, or sham stimulation, for a period of one hour. To assess the effects of stimulation on blood glucose and glucoregulatory hormones, blood samples were drawn before, during and after stimulation. Subsequently, all animals were used for quantitative assessment of Fos immunoreactivity in the lateral hypothalamic area (LHA using computerized image analysis. DBS of the sNAc rapidly increased plasma concentrations of glucagon and glucose while sham stimulation and DBS outside the sNAc were ineffective. In addition, the increase in glucose was dependent on DBS intensity. In contrast, the DBS-induced increase in plasma corticosterone concentrations was independent of intensity and region, indicating that the observed DBS-induced metabolic changes were not due to corticosterone release. Stimulation of the sNAc with 200 μA increased Fos immunoreactivity in the LHA compared to sham or 100 μA stimulated animals. These data show that DBS of the sNAc alters glucose metabolism in a region- and intensity dependent manner in association with neuronal activation in the LHA. Moreover, these data illustrate the need to monitor changes in glucose metabolism during DBS-treatment of OCD patients.

  1. Deep thiopental anesthesia alters steady-state glucose homeostasis but not the neurochemical profile of rat cortex.

    Science.gov (United States)

    Lei, Hongxia; Duarte, Joao M N; Mlynarik, Vladimir; Python, Agathe; Gruetter, Rolf

    2010-02-01

    Barbiturates are regularly used as an anesthetic for animal experimentation and clinical procedures and are frequently provided with solubilizing compounds, such as ethanol and propylene glycol, which have been reported to affect brain function and, in the case of (1)H NMR experiments, originate undesired resonances in spectra affecting the quantification. As an alternative, thiopental can be administrated without any solubilizing agents. The aim of the study was to investigate the effect of deep thiopental anesthesia on the neurochemical profile consisting of 19 metabolites and on glucose transport kinetics in vivo in rat cortex compared with alpha-chloralose using localized (1)H NMR spectroscopy. Thiopental was devoid of effects on the neurochemical profile, except for the elevated glucose at a given plasma glucose level resulting from thiopental-induced depression of glucose consumption at isoelectrical condition. Over the entire range of plasma glucose levels, steady-state glucose concentrations were increased on average by 48% +/- 8%, implying that an effect of deep thiopental anesthesia on the transport rate relative to cerebral glucose consumption ratio was increased by 47% +/- 8% compared with light alpha-chloralose-anesthetized rats. We conclude that the thiopental-induced isoelectrical condition in rat cortex significantly affected glucose contents by depressing brain metabolism, which remained substantial at isoelectricity. 2009 Wiley-Liss, Inc.

  2. Homeostatic effect of p-chloro-diphenyl diselenide on glucose metabolism and mitochondrial function alterations induced by monosodium glutamate administration to rats.

    Science.gov (United States)

    Quines, Caroline B; Rosa, Suzan G; Chagas, Pietro M; da Rocha, Juliana T; Dobrachinski, Fernando; Carvalho, Nélson R; Soares, Félix A; da Luz, Sônia C Almeida; Nogueira, Cristina W

    2016-01-01

    The metabolic syndrome is a group of metabolic alterations considered a worldwide public health problem. Organic selenium compounds have been reported to have many different pharmacological actions, such as anti-hypercholesterolemic and anti-hyperglycemic. The aim of this study was to evaluate the effect of p-chloro-diphenyl diselenide (p-ClPhSe)2, an organic selenium compound, in a model of obesity induced by monosodium glutamate (MSG) administration in rats. The rats were treated during the first ten postnatal days with MSG and received (p-ClPhSe)2 (10 mg/kg, intragastrically) from 45th to 51 th postnatal day. Glucose, lipid and lactate levels were determined in plasma of rats. Glycogen levels and activities of tyrosine aminotransferase, hexokinase, citrate synthase and glucose-6-phosphatase (G-6-Pase) were determined in livers of rats. Renal G-6-Pase activity was also determined. The purine content [Adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate] and mitochondrial functionality in the liver were also investigated. p-(ClPhSe)2 did not alter the reduction in growth performance and in the body weight caused by MSG but reduced epididymal fat deposition of rats. p-(ClPhSe)2 restored glycemia, triglycerides, cholesterol and lactate levels as well as the glucose metabolism altered in rats treated with MSG. p-(ClPhSe)2 restored hepatic mitochondrial dysfunction and the decrease in citrate synthase activity and ATP and ADP levels caused by MSG in rats. In summary, (p-ClPhSe)2 had homeostatic effects on glucose metabolism and mitochondrial function alterations induced by MSG administration to rats.

  3. Opportunity Cost and Policy: A Utilization Review of Self-monitoring of Blood Glucose in Manitoba, Canada.

    Science.gov (United States)

    Serwylo, Olena; Friesen, Kevin; Falk, Jamie; Bugden, Shawn

    2016-04-01

    Recently, there has been a re-evaluation of the frequency, benefits, and costs associated with self-monitoring of blood glucose (SMBG). Based on little evidence of the benefit of frequent SMBG in patients with diabetes not using insulin, new guidelines and test strip limit policies have been suggested and implemented in various Canadian jurisdictions to promote a more selective practice of SMBG. The objective of this study was to assess the overall utilization and cost associated with test strips and lancets for SMBG in Manitoba from 2000 to 2013 as well as to explore the policy implications of the implementation of test strip quantity limits and its impact on overall and government costs. An analysis of prescription claims for blood glucose test strips (BGTSs) and lancets for all patients with diabetes in Manitoba from 2000 to 2013 was conducted. In each year, patients were stratified into 4 mutually exclusive hierarchical groups according to most intensive diabetes treatment. Test strip and lancet utilization and cost were assessed for each group in each year, and the potential cost savings associated with implementation of a BGTS limit policy was projected using autoregressive integrated moving average models. In the year 2000, 8 million test strips were dispensed in Manitoba, increasing by 170% to 21.7 million test strips in 2013. Insulin users accounted for the majority of test strip use. However, based on potential implementation of test strip limit policies, 95% of the reduction of test strip use is predicted to occur in the groups not using insulin. Based on current trends, the 5-year predicted additional cost associated with not implementing a test strip limit policy similar to that implemented in other Canadian provinces was estimated to be a total of $12.35 million. Implementation of the guideline-based policy limits is predicted to produce considerable savings, with 95% of potential savings occurring in patients not using insulin. There is, therefore, a

  4. Chronic exposure of HIT cells to high glucose concentrations paradoxically decreases insulin gene transcription and alters binding of insulin gene regulatory protein.

    Science.gov (United States)

    Olson, L K; Redmon, J B; Towle, H C; Robertson, R P

    1993-07-01

    Chronically culturing HIT-T15 cells in media containing high glucose concentrations leads to decreased insulin mRNA levels, insulin content, and insulin secretion. These changes can be prevented by culturing the cells in media containing lower glucose levels (Robertson, R. P., H.-J. Zhang, K. L. Pyzdrowski, and T. F. Walseth. 1992. J. Clin. Invest. 90:320-325). The mechanism of this seemingly paradoxical phenomenon was examined by transiently transfecting HIT cells with a chloramphenicol acetyl transferase (CAT) reporter gene controlled by the 5'-regulatory domain of the human insulin gene (INSCAT). Early passages of HIT cells readily expressed INSCAT, whereas late passages of cells chronically cultured in 11.1 mM glucose expressed only 28.7 +/- 2.3% (mean +/- SEM) of the CAT activity expressed in early passages. In contrast, late passages of HIT cells chronically cultured in 0.8 mM glucose retained the ability to express the INSCAT reporter gene to 69.6 +/- 10.0% of the CAT activity observed in early passages. The decrease in INSCAT expression in late passages of cells serially cultured in 11.1 mM glucose was associated with the inability to form a specific nuclear protein-DNA complex with the CT motifs of the human insulin promoter. Formation of this specific protein-DNA complex was preserved in late passages of HIT cells when serially cultured in 0.8 mM glucose. Mutations of the CT motifs caused markedly diminished CAT activity in all passages examined. These data indicate that chronic exposure of the beta cell to high glucose concentrations can paradoxically decrease insulin gene transcription, in part, by altering the ability of a regulatory protein (GSTF) to interact with the insulin gene promoter. This provides a potential mechanism for glucotoxic effects on the beta cell at the level of the insulin gene.

  5. Co-utilization of glucose and xylose by evolved Thermus thermophilus LC113 strain elucidated by 13C metabolic flux analysis and whole genome sequencing

    Science.gov (United States)

    Cordova, Lauren T.; Lu, Jing; Cipolla, Robert M.; Sandoval, Nicholas R.; Long, Christopher P.; Antoniewicz, Maciek R.

    2018-01-01

    We evolved Thermus thermophilus to efficiently co-utilize glucose and xylose, the two most abundant sugars in lignocellulosic biomass, at high temperatures without carbon catabolite repression. To generate the strain, T. thermophilus HB8 was first evolved on glucose to improve its growth characteristics, followed by evolution on xylose. The resulting strain, T. thermophilus LC113, was characterized in growth studies, by whole genome sequencing, and 13C-metabolic flux analysis (13C-MFA) with [1,6-13C]glucose, [5-13C]xylose, and [1,6-13C]glucose + [5-13C]xylose as isotopic tracers. Compared to the starting strain, the evolved strain had an increased growth rate (~ 2-fold), increased biomass yield, increased tolerance to high temperatures up to 90 °C, and gained the ability to grow on xylose in minimal medium. At the optimal growth temperature of 81 °C, the maximum growth rate on glucose and xylose was 0.44 and 0.46 h−1, respectively. In medium containing glucose and xylose the strain efficiently co-utilized the two sugars. 13C-MFA results provided insights into the metabolism of T. thermophilus LC113 that allows efficient co-utilization of glucose and xylose. Specifically, 13C-MFA revealed that metabolic fluxes in the upper part of metabolism adjust flexibly to sugar availability, while fluxes in the lower part of metabolism remain relatively constant. Whole genome sequence analysis revealed two large structural changes that can help explain the physiology of the evolved strain: a duplication of a chromosome region that contains many sugar transporters, and a 5× multiplication of a region on the pVV8 plasmid that contains xylose isomerase and xylulokinase genes, the first two enzymes of xylose catabolism. Taken together, 13C-MFA and genome sequence analysis provided complementary insights into the physiology of the evolved strain. PMID:27164561

  6. Simultaneous coffee caffeine intake and sleep deprivation alter glucose homeostasis in Iranian men: a randomized crossover trial.

    Science.gov (United States)

    Rasaei, Behrouz; Talib, Ruzita Abd; Noor, Mohd Ismail; Karandish, Majid; Karim, Norimah A

    2016-12-01

    Sleep deprivation and coffee caffeine consumption have been shown to affect glucose homeostasis separately, but the combined effects of these two variables are unknown. Forty-two healthy Iranian men, aged 20-40 years old, were assigned to three groups in a randomised crossover trial involving three treatments with two-week washout periods. Subjects were moderate coffee consumers (Sleep Quality Index sleep (4 hrs. in bed) plus 3×150 cc/cup of boiled water (BW treatment), decaffeinated coffee (DC treatment, without sugar, 99.9% caffeine-free), and caffeinated coffee (CC treatment, without sugar, 65 mg caffeine/ cup). DC and CC treatments were blinded. At the end of each treatment, fasting serum glucose (using enzyme assays) and insulin (using electrochemiluminescence immunoassay) were measured and, again, two hours after an oral glucose tolerance test (OGTT). Insulin resistance was quantified with the homeostasis model. Repeated measures ANOVA indicated no significant difference between the treatments in fasting serum glucose (p=0.248) or insulin resistance (p=0.079). However, ANOVA demonstrated differences between treatments in fasting serum insulin (p=0.004) and glucose, as well as insulin after OGTT (pcaffeinated coffee was more adverse for glucose homeostasis compared to decaffeinated coffee in individuals who were simultaneously sleep deprived.

  7. Transcriptional Modulation of Transport- and Metabolism-Associated Gene Clusters Leading to Utilization of Benzoate in Preference to Glucose in Pseudomonas putida CSV86.

    Science.gov (United States)

    Choudhary, Alpa; Modak, Arnab; Apte, Shree K; Phale, Prashant S

    2017-10-01

    The effective elimination of xenobiotic pollutants from the environment can be achieved by efficient degradation by microorganisms even in the presence of sugars or organic acids. Soil isolate Pseudomonas putida CSV86 displays a unique ability to utilize aromatic compounds prior to glucose. The draft genome and transcription analyses revealed that glucose uptake and benzoate transport and metabolism genes are clustered at the glc and ben loci, respectively, as two distinct operons. When grown on glucose plus benzoate, CSV86 displayed significantly higher expression of the ben locus in the first log phase and of the glc locus in the second log phase. Kinetics of substrate uptake and metabolism matched the transcription profiles. The inability of succinate to suppress benzoate transport and metabolism resulted in coutilization of succinate and benzoate. When challenged with succinate or benzoate, glucose-grown cells showed rapid reduction in glc locus transcription, glucose transport, and metabolic activity, with succinate being more effective at the functional level. Benzoate and succinate failed to interact with or inhibit the activities of glucose transport components or metabolic enzymes. The data suggest that succinate and benzoate suppress glucose transport and metabolism at the transcription level, enabling P. putida CSV86 to preferentially metabolize benzoate. This strain thus has the potential to be an ideal host to engineer diverse metabolic pathways for efficient bioremediation. IMPORTANCE Pseudomonas strains play an important role in carbon cycling in the environment and display a hierarchy in carbon utilization: organic acids first, followed by glucose, and aromatic substrates last. This limits their exploitation for bioremediation. This study demonstrates the substrate-dependent modulation of ben and glc operons in Pseudomonas putida CSV86, wherein benzoate suppresses glucose transport and metabolism at the transcription level, leading to preferential

  8. Altered Expression of Somatostatin Receptors in Pancreatic Islets from NOD Mice Cultured at Different Glucose Concentrations In Vitro and in Islets Transplanted to Diabetic NOD Mice In Vivo

    Directory of Open Access Journals (Sweden)

    Eva Ludvigsen

    2011-01-01

    Full Text Available Somatostatin acts via five receptors (sst1-5. We investigated if the changes in pancreatic islet sst expression in diabetic NOD mice compared to normoglycemic mice are a consequence of hyperglycemia or the ongoing immune reaction in the pancreas. Pancreatic islets were isolated from NOD mice precultured for 5 days and further cultured for 3 days at high or low glucose before examined. Islets were also isolated from NOD mice and transplanted to normal or diabetic mice in a number not sufficient to cure hyperglycemia. After three days, the transplants were removed and stained for sst1-5 and islet hormones. Overall, changes in sst islet cell expression were more common in islets cultured in high glucose concentration in vitro as compared to the islet transplantation in vivo to diabetic mice. The beta and PP cells exhibited more frequent changes in sst expression, while the alpha and delta cells were relatively unaffected by the high glucose condition. Our findings suggest that the glucose level may alter sst expressed in islets cells; however, immune mechanisms may counteract such changes in islet sst expression.

  9. Glucose Transporters in Cardiac Metabolism and Hypertrophy

    Science.gov (United States)

    Shao, Dan; Tian, Rong

    2016-01-01

    The heart is adapted to utilize all classes of substrates to meet the high-energy demand, and it tightly regulates its substrate utilization in response to environmental changes. Although fatty acids are known as the predominant fuel for the adult heart at resting stage, the heart switches its substrate preference toward glucose during stress conditions such as ischemia and pathological hypertrophy. Notably, increasing evidence suggests that the loss of metabolic flexibility associated with increased reliance on glucose utilization contribute to the development of cardiac dysfunction. The changes in glucose metabolism in hypertrophied hearts include altered glucose transport and increased glycolysis. Despite the role of glucose as an energy source, changes in other nonenergy producing pathways related to glucose metabolism, such as hexosamine biosynthetic pathway and pentose phosphate pathway, are also observed in the diseased hearts. This article summarizes the current knowledge regarding the regulation of glucose transporter expression and translocation in the heart during physiological and pathological conditions. It also discusses the signaling mechanisms governing glucose uptake in cardiomyocytes, as well as the changes of cardiac glucose metabolism under disease conditions. PMID:26756635

  10. Targeting Hydrothermal Alterations Utilizing LANDSAT-8 Andaster Data in Shahr-E Iran

    Science.gov (United States)

    Safari, M.; Pour, A. B.; Maghsoudi, A.; Hashim, M.

    2017-10-01

    Shahr-e-Babak tract of the Kerman metalogenic belt is one of the most potential segments of Urumieh-Dokhtar (Sahand-Bazman) magmatic arc. This area encompasses several porphyry copper deposits in exploration, development and exploitation hierarchy. The aim of this study is to map hydrothermal alterations caused by early Cenozoic magmatic intrusions in Shahr-e-Babak area. To this purpose, mineral mapping methods including band combinations, ratios and multiplications as well as PCA and MNF data space transforms in SWIR and VNIR for both ASTER and OLI sensors. Alteration zones according to spectral signatures of each type of alteration mineral assemblages such as argillic, phyllic and propylitic are successfully mapped. For enhancing the target areas false color composites and HSI-RGB color space transform are performed on developed band combinations. Previous studies have proven the robust application of ASTER in geology and mineral exploration; nonetheless, the results of this investigation prove applicability of OLI sensor from landsat-8 for alteration mapping. According to the results, evidently OLI sensor data can accurately map alteration zones. Additionally, the 12-bit quantization of OLI data is its privilege over 8-bit data of ASTER in VNIR and SWIR, thus OLI high quality results, which makes it easy to distinguish targets with enhanced color contrast between the altered and unaltered rocks.

  11. TARGETING HYDROTHERMAL ALTERATIONS UTILIZING LANDSAT-8 ANDASTER DATA IN SHAHR-E-BABAK, IRAN

    Directory of Open Access Journals (Sweden)

    M. Safari

    2017-10-01

    Full Text Available Shahr-e-Babak tract of the Kerman metalogenic belt is one of the most potential segments of Urumieh–Dokhtar (Sahand-Bazman magmatic arc. This area encompasses several porphyry copper deposits in exploration, development and exploitation hierarchy. The aim of this study is to map hydrothermal alterations caused by early Cenozoic magmatic intrusions in Shahr-e-Babak area. To this purpose, mineral mapping methods including band combinations, ratios and multiplications as well as PCA and MNF data space transforms in SWIR and VNIR for both ASTER and OLI sensors. Alteration zones according to spectral signatures of each type of alteration mineral assemblages such as argillic, phyllic and propylitic are successfully mapped. For enhancing the target areas false color composites and HSI-RGB color space transform are performed on developed band combinations. Previous studies have proven the robust application of ASTER in geology and mineral exploration; nonetheless, the results of this investigation prove applicability of OLI sensor from landsat-8 for alteration mapping. According to the results, evidently OLI sensor data can accurately map alteration zones. Additionally, the 12-bit quantization of OLI data is its privilege over 8-bit data of ASTER in VNIR and SWIR, thus OLI high quality results, which makes it easy to distinguish targets with enhanced color contrast between the altered and unaltered rocks.

  12. Measurement of glucose utilization by Pseudomonas fluorescens that are free-living and that are attached to surfaces

    International Nuclear Information System (INIS)

    Fletcher, M.

    1986-01-01

    The assimilation and respiration of glucose by attached and free-living Pseudomonas fluorescens were compared. The attachment surfaces were polyvinylidene fluoride, polyethylene, and glass. Specific uptake of [ 1 C]glucose was determined after bacterial biomass was measured by (1) microscopic counts or (2) prelabelling of cells by providing [ 3 H]leucine as substrate, followed by dual-labelling scintillation counting. The glucose concentration was 1.4, 3.5, 5.5, 7.6, or 9.7 μM. Glucose assimilation by cells which became detached from the surfaces during incubation with glucose was also measured after the detached cells were collected by filtration. The composition of the substratum had no effect on the amount of glucose assimilated by attached cells. Glucose assimilation by attached cells exceeded that by free-living cells by a factor of between 2 and 5 or more, and respiration of glucose by surface-associated cells was greater than that by free-living bacteria. Glucose assimilation by detached cells was greater than that by attached bacteria. Measurements of biomass by microscopic counts gave more consistent results than those obtained with dual-labelling, but in general, results obtained by both methods were corroborative

  13. 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.

  14. Transgenerational Glucose Intolerance of Tumor Necrosis Factor with Epigenetic Alteration in Rat Perirenal Adipose Tissue Induced by Intrauterine Hyperglycemia.

    Science.gov (United States)

    Su, Rina; Yan, Jie; Yang, Huixia

    2016-01-01

    Changes in DNA methylation may play a role in the genetic mechanism underlying glucose intolerance in the offspring of mothers with diabetes. Here, we established a rat model of moderate intrauterine hyperglycemia induced by streptozotocin to detect glucose and lipid metabolism of first-generation (F1) and second-generation (F2) offspring. Moderate intrauterine hyperglycemia induced high body weight in F1 and F2 offspring of diabetic mothers. F1 offspring had impaired glucose tolerance and abnormal insulin level. Additionally, F1 and F2 offspring that were exposed to intrauterine hyperglycemia had impaired insulin secretion from the islets. The tumor necrosis factor (Tnf) gene was upregulated in perirenal adipose tissue from F1 offspring and relatively increased in F2 offspring. Both F1 and F2 offspring showed similar hypomethylation level at the -1952 site of Tnf. We confirmed that DNA methylation occurs in offspring exposed to intrauterine hyperglycemia and that the DNA methylation is intergenerational and inherited.

  15. Neuronal glucose but not lactate utilization is positively correlated with NMDA-induced neurotransmission and fluctuations in cytosolic Ca2+ levels

    DEFF Research Database (Denmark)

    Bak, Lasse K; Walls, Anne B; Schousboe, Arne

    2009-01-01

    release in cultured cerebellar neurons from mice. Pulses of NMDA at 30, 100, and 300 microM, leading to a progressive increase in both cytosolic [Ca2+] and release of glutamate, increased uptake and metabolism of glucose but not that of lactate as evidenced by mass spectrometric measurement of 13C...... incorporation into intracellular glutamate. In this manuscript, a cascade of events for the preferential neuronal utilization of glucose during neurotransmission is suggested and discussed in relation to our current understanding of neuronal energy metabolism....

  16. Dietary soya protein improves intra-myocardial lipid deposition and altered glucose metabolism in a hypertensive, dyslipidaemic, insulin-resistant rat model.

    Science.gov (United States)

    Oliva, María E; Creus, Agustina; Ferreira, María R; Chicco, Adriana; Lombardo, Yolanda B

    2018-01-01

    This study investigates the effects of replacing dietary casein by soya protein on the underlying mechanisms involved in the impaired metabolic fate of glucose and lipid metabolisms in the heart of dyslipidaemic rats chronically fed (8 months) a sucrose-rich (62·5 %) diet (SRD). To test this hypothesis, Wistar rats were fed an SRD for 4 months. From months 4 to 8, half the animals continued with the SRD and the other half were fed an SRD in which casein was substituted by soya. The control group received a diet with maize starch as the carbohydrate source. Compared with the SRD-fed group, the following results were obtained. First, soya protein significantly (Psoya protein significantly increased (Psoya protein upon the altered pathways of glucose and lipid metabolism in the heart muscle of this rat model.

  17. Alterations in body weight and blood glucose level of female hamsters exposed to electromagnetic fields of cell phones

    Directory of Open Access Journals (Sweden)

    A.R Lotfi

    2010-02-01

    Group 2 was exposed to electromagnetic field emitted by cell phones for 10 days (short term and group 3 for 50 day (long term. In the latter groups, the exposure was 1 hour per day. At the end of the experimental period, the animals were weighed and blood glucose concentrations were determined by obtaining blood samples from 8 randomly selected hamsters in each group.  The blood glucose level was significantly higher in long-term exposed group in comparison with the control and short-term exposed groups (175, 11.6 and 107 mg/dl, respectively (p

  18. Association of improved oxidative stress tolerance and alleviation of glucose repression with superior xylose-utilization capability by a natural isolate ofSaccharomyces cerevisiae.

    Science.gov (United States)

    Cheng, Cheng; Tang, Rui-Qi; Xiong, Liang; Hector, Ronald E; Bai, Feng-Wu; Zhao, Xin-Qing

    2018-01-01

    Saccharomyces cerevisiae wild strains generally have poor xylose-utilization capability, which is a major barrier for efficient bioconversion of lignocellulosic biomass. Laboratory adaption is commonly used to enhance xylose utilization of recombinant S. cerevisiae . Apparently, yeast cells could remodel the metabolic network for xylose metabolism. However, it still remains unclear why natural isolates of S. cerevisiae poorly utilize xylose. Here, we analyzed a unique S. cerevisiae natural isolate YB-2625 which has superior xylose metabolism capability in the presence of mixed-sugar. Comparative transcriptomic analysis was performed using S. cerevisiae YB-2625 grown in a mixture of glucose and xylose, and the model yeast strain S288C served as a control. Global gene transcription was compared at both the early mixed-sugar utilization stage and the latter xylose-utilization stage. Genes involved in endogenous xylose-assimilation ( XYL2 and XKS1 ), gluconeogenesis, and TCA cycle showed higher transcription levels in S. cerevisiae YB-2625 at the xylose-utilization stage, when compared to the reference strain. On the other hand, transcription factor encoding genes involved in regulation of glucose repression ( MIG1 , MIG2 , and MIG3 ) as well as HXK2 displayed decreased transcriptional levels in YB-2625, suggesting the alleviation of glucose repression of S. cerevisiae YB-2625. Notably, genes encoding antioxidant enzymes ( CTT1 , CTA1 , SOD2, and PRX1 ) showed higher transcription levels in S. cerevisiae YB-2625 in the xylose-utilization stage than that of the reference strain. Consistently, catalase activity of YB-2625 was 1.9-fold higher than that of S. cerevisiae S288C during the xylose-utilization stage. As a result, intracellular reactive oxygen species levels of S. cerevisiae YB-2625 were 43.3 and 58.6% lower than that of S288C at both sugar utilization stages. Overexpression of CTT1 and PRX1 in the recombinant strain S. cerevisiae YRH396 deriving from S

  19. Simultaneous, quantitative measurement of local blood flow and glucose utilization in tissue samples in normal and injured feline brain.

    Science.gov (United States)

    DeWitt, D S; Yuan, X Q; Becker, D P; Hayes, R L

    1988-01-01

    Cerebral blood flow (CBF) and local cerebral glucose utilization (LCGU) were measured using radioactive microspheres and [14C]2-deoxyglucose, respectively, in 26 brain regions in control animals (n = 8) and in animals (n = 4) sustaining low-level experimental brain injury. Examination of the initial (resting) CBF measurement in the uninjured cats revealed two subgroups with significantly (p less than 0.01) different CBF levels. In uninjured cats with normal CBF levels (33.4 +/- 1.8 ml/100 g/min) there was a close linear relationship between CBF and LCGU (n = 0.71, p less than 0.01). In contrast, the remainder of the uninjured cats exhibited abnormally high levels of CBF (72.6 +/- 9.9 ml/100 g/min) and the absence of a close relationship between CBF and LCGU (r = 0.27). One hour following low-level (2.0 atm) fluid percussion brain injury, CBF was increased and LCGU was decreased, though not significantly. The relationship between CBF and LCGU remained intact (r = 0.66, p less than 0.01) in most brain regions. However, the relationship between CBF and LCGU in the hippocampus differed significantly from the relationship between the two parameters in the rest of the brain. Thus, the use of the radioactive microsphere method for CBF measurements allows multiple measurements of CBF and permits the assessment of the status of the cerebral vasculature prior to experimental manipulations such as traumatic brain injury. In view of our current findings of an abnormal relationship between CBF and LCGU in cats with high resting CBF levels, this is an important advantage. In addition, the combination of the microsphere and 2-DG techniques within the same tissue samples allows for the investigation of the effects of traumatic injury on the important relationship between CBF and LCGU.

  20. Patterns, Policy and Appropriateness: A 12-Year Utilization Review of Blood Glucose Test Strip Use in Insulin Users.

    Science.gov (United States)

    Falk, Jamie; Friesen, Kevin J; Okunnu, Anuoluwapo; Bugden, Shawn

    2017-08-01

    Considerable attention has been paid to the rising costs of the use of blood glucose test strips (BGTS). Insulin users have generally been treated as a single homogeneous group, resulting in policies that cap usage (8.2 strips/day) in provincial drug insurance programs. The objective of this study was to conduct a utilization review of BGTS by insulin users and to evaluate use patterns against current insulin use patterns and BGTS policy. BGTS usage was examined in a cohort of insulin users with type 1 and type 2 diabetes over a 12-year period (2001 to 2013) using the population-based administrative data in Manitoba, Canada. Total BGTS strip use increased by 121%, from $4.3 to $9.5 million. However, the number of insulin users also increased by 115%. Use has been stable at 1.5 strips per day per person since 2004 by insulin users with type 2 diabetes but has risen from 1.9 to 3.0 strips per day per person in those with type 1 diabetes. Mean daily test strip use was below the number of daily tests recommended for patients using insulin as per the current Canadian guidelines, with 11% and 15% of insulin users with type 1 and type 2 diabetes not claiming any BGTS use and a further 15% (type 1) and 28% (type 2) using fewer than 1 strip per day. BGTS use per insulin user has been stable for most of the past decade, and the vast majority of use falls well below provincial insurance caps. The amount of low-level testing (0 to <1 strip/day) suggests that greater attention should be directed to ensuring a safe level of testing by all insulin users. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Coffee Consumption, Newly Diagnosed Diabetes, and Other Alterations in Glucose Homeostasis: A Cross-Sectional Analysis of the Longitudinal Study of Adult Health (ELSA-Brasil)

    Science.gov (United States)

    Yarmolinsky, James; Mueller, Noel T.; Duncan, Bruce B.; Bisi Molina, Maria del Carmen; Goulart, Alessandra C.; Schmidt, Maria Inês

    2015-01-01

    Introduction Observational studies have reported fairly consistent inverse associations between coffee consumption and risk of type 2 diabetes, but this association has been little investigated with regard to lesser degrees of hyperglycemia and other alterations in glucose homeostasis. Additionally, the association between coffee consumption and diabetes has been rarely investigated in South American populations. We examined the cross-sectional relationships of coffee intake with newly diagnosed diabetes and measures of glucose homeostasis, insulin sensitivity, and insulin secretion, in a large Brazilian cohort of middle-aged and elderly individuals. Methods We used baseline data from 12,586 participants of the Longitudinal Study of Adult Health (ELSA-Brasil). Logistic regression analyses were performed to examine associations between coffee consumption and newly diagnosed diabetes. Analysis of covariance was used to assess coffee intake in relation to two-hour glucose from an oral glucose tolerance test, fasting glucose, glycated hemoglobin, fasting and –2-hour postload insulin and measures of insulin sensitivity. Results We found an inverse association between coffee consumption and newly diagnosed diabetes, after adjusting for multiple covariates [23% and 26% lower odds of diabetes for those consuming coffee 2–3 and >3 times per day, respectively, compared to those reporting never or almost never consuming coffee, (p = .02)]. An inverse association was also found for 2-hour postload glucose [Never/almost never: 7.57 mmol/L, ≤1 time/day: 7.48 mmol/L, 2-3 times/day: 7.22 mmol/L, >3 times/day: 7.12 mol/L, pCoffee was additionally associated with 2-hour postload insulin [Never/almost never: 287.2 pmol/L, ≤1 time/day: 280.1 pmol/L, 2–3 times/day: 275.3 pmol/L, >3 times/day: 262.2 pmol/L, p = 0.0005) but not with fasting insulin concentrations (p = .58). Conclusion Our present study provides further evidence of a protective effect of coffee on risk of adult

  2. Utilizing distributional analytics and electronic records to assess timeliness of inpatient blood glucose monitoring in non-critical care wards.

    Science.gov (United States)

    Chen, Ying; Kao, Shih Ling; Tai, E-Shyong; Wee, Hwee Lin; Khoo, Eric Yin Hao; Ning, Yilin; Salloway, Mark Kevin; Deng, Xiaodong; Tan, Chuen Seng

    2016-04-08

    Regular and timely monitoring of blood glucose (BG) levels in hospitalized patients with diabetes mellitus is crucial to optimizing inpatient glycaemic control. However, methods to quantify timeliness as a measurement of quality of care are lacking. We propose an analytical approach that utilizes BG measurements from electronic records to assess adherence to an inpatient BG monitoring protocol in hospital wards. We applied our proposed analytical approach to electronic records obtained from 24 non-critical care wards in November and December 2013 from a tertiary care hospital in Singapore. We applied distributional analytics to evaluate daily adherence to BG monitoring timings. A one-sample Kolmogorov-Smirnov (1S-KS) test was performed to test daily BG timings against non-adherence represented by the uniform distribution. This test was performed among wards with high power, determined through simulation. The 1S-KS test was coupled with visualization via the cumulative distribution function (cdf) plot and a two-sample Kolmogorov-Smirnov (2S-KS) test, enabling comparison of the BG timing distributions between two consecutive days. We also applied mixture modelling to identify the key features in daily BG timings. We found that 11 out of the 24 wards had high power. Among these wards, 1S-KS test with cdf plots indicated adherence to BG monitoring protocols. Integrating both 1S-KS and 2S-KS information within a moving window consisting of two consecutive days did not suggest frequent potential change from or towards non-adherence to protocol. From mixture modelling among wards with high power, we consistently identified four components with high concentration of BG measurements taken before mealtimes and around bedtime. This agnostic analysis provided additional evidence that the wards were adherent to BG monitoring protocols. We demonstrated the utility of our proposed analytical approach as a monitoring tool. It provided information to healthcare providers regarding

  3. Utilizing distributional analytics and electronic records to assess timeliness of inpatient blood glucose monitoring in non-critical care wards

    Directory of Open Access Journals (Sweden)

    Ying Chen

    2016-04-01

    Full Text Available Abstract Background Regular and timely monitoring of blood glucose (BG levels in hospitalized patients with diabetes mellitus is crucial to optimizing inpatient glycaemic control. However, methods to quantify timeliness as a measurement of quality of care are lacking. We propose an analytical approach that utilizes BG measurements from electronic records to assess adherence to an inpatient BG monitoring protocol in hospital wards. Methods We applied our proposed analytical approach to electronic records obtained from 24 non-critical care wards in November and December 2013 from a tertiary care hospital in Singapore. We applied distributional analytics to evaluate daily adherence to BG monitoring timings. A one-sample Kolmogorov-Smirnov (1S-KS test was performed to test daily BG timings against non-adherence represented by the uniform distribution. This test was performed among wards with high power, determined through simulation. The 1S-KS test was coupled with visualization via the cumulative distribution function (cdf plot and a two-sample Kolmogorov-Smirnov (2S-KS test, enabling comparison of the BG timing distributions between two consecutive days. We also applied mixture modelling to identify the key features in daily BG timings. Results We found that 11 out of the 24 wards had high power. Among these wards, 1S-KS test with cdf plots indicated adherence to BG monitoring protocols. Integrating both 1S-KS and 2S-KS information within a moving window consisting of two consecutive days did not suggest frequent potential change from or towards non-adherence to protocol. From mixture modelling among wards with high power, we consistently identified four components with high concentration of BG measurements taken before mealtimes and around bedtime. This agnostic analysis provided additional evidence that the wards were adherent to BG monitoring protocols. Conclusions We demonstrated the utility of our proposed analytical approach as a monitoring

  4. A metabolic core model elucidates how enhanced utilization of glucose and glutamine, with enhanced glutamine-dependent lactate production, promotes cancer cell growth: The WarburQ effect.

    Science.gov (United States)

    Damiani, Chiara; Colombo, Riccardo; Gaglio, Daniela; Mastroianni, Fabrizia; Pescini, Dario; Westerhoff, Hans Victor; Mauri, Giancarlo; Vanoni, Marco; Alberghina, Lilia

    2017-09-01

    Cancer cells share several metabolic traits, including aerobic production of lactate from glucose (Warburg effect), extensive glutamine utilization and impaired mitochondrial electron flow. It is still unclear how these metabolic rearrangements, which may involve different molecular events in different cells, contribute to a selective advantage for cancer cell proliferation. To ascertain which metabolic pathways are used to convert glucose and glutamine to balanced energy and biomass production, we performed systematic constraint-based simulations of a model of human central metabolism. Sampling of the feasible flux space allowed us to obtain a large number of randomly mutated cells simulated at different glutamine and glucose uptake rates. We observed that, in the limited subset of proliferating cells, most displayed fermentation of glucose to lactate in the presence of oxygen. At high utilization rates of glutamine, oxidative utilization of glucose was decreased, while the production of lactate from glutamine was enhanced. This emergent phenotype was observed only when the available carbon exceeded the amount that could be fully oxidized by the available oxygen. Under the latter conditions, standard Flux Balance Analysis indicated that: this metabolic pattern is optimal to maximize biomass and ATP production; it requires the activity of a branched TCA cycle, in which glutamine-dependent reductive carboxylation cooperates to the production of lipids and proteins; it is sustained by a variety of redox-controlled metabolic reactions. In a K-ras transformed cell line we experimentally assessed glutamine-induced metabolic changes. We validated computational results through an extension of Flux Balance Analysis that allows prediction of metabolite variations. Taken together these findings offer new understanding of the logic of the metabolic reprogramming that underlies cancer cell growth.

  5. 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...

  6. Prevalence of diabetes mellitus and impaired glucose tolerance in patients with decompensated cirrhosis being evaluated for liver transplantation: the utility of oral glucose tolerance test

    Directory of Open Access Journals (Sweden)

    Ana Carolina Costa Bragança

    2010-03-01

    Full Text Available CONTEXT: Cirrhosis, diabetes mellitus, impaired glucose tolerance, insulin resistance, and protein calorie malnutrition are important issues in cirrhotic patients because they can increase the progression of liver disease and worsen its prognosis. OBJECTIVE:To determine the prevalence of diabetes mellitus, impaired glucose tolerance and insulin resistance in cirrhotic patients being evaluated for liver transplantation and their impacts on a 3-month follow-up, and to compare fasting glycemia and oral glucose tolerance test. METHODS: A cross-sectional study was performed in consecutively included adult patients. Diabetes mellitus was established through fasting glycemia and oral glucose tolerance test in diagnosing diabetes mellitus in this population. HOMA-IR and HOMA-β indexes were calculated, and nutritional assessment was performed by subjective global assessment, anthropometry and handgrip strength through dynamometry. RESULTS: Diabetes mellitus was found in 40 patients (64.5%, 9 (22.5% of them by fasting glycemia and 31 (77.5% of them by oral glucose tolerance test. Insulin resistance was found in 40 (69% of the patients. There was no relationship between diabetes mellitus and the etiology of cirrhosis. Protein calorie malnutrition was diagnosed in a range from 3.22% to 45.2% by anthropometry, 58.1% by subjective global assessment and 88.7% by handgrip strength. Diabetes mellitus identified by oral glucose tolerance test was related significantly to a higher prevalence of infectious complications and deaths in a 3-month period (P = 0.017. CONCLUSION: The prevalence of diabetes mellitus, impaired glucose tolerance, insulin resistance and protein calorie malnutrition is high in cirrhotic patients on the waiting list for liver transplantation. There were more infectious complications and/or deaths in a 3-month follow-up period in patients with diabetes mellitus diagnosed by oral glucose tolerance test. Oral glucose tolerance test seems to be

  7. Partial inhibition of adipose tissue lipolysis improves glucose metabolism and insulin sensitivity without alteration of fat mass.

    Directory of Open Access Journals (Sweden)

    Amandine Girousse

    Full Text Available When energy is needed, white adipose tissue (WAT provides fatty acids (FAs for use in peripheral tissues via stimulation of fat cell lipolysis. FAs have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL participates in the breakdown of WAT triacylglycerol into FAs. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight, fat mass, and WAT inflammation in high-fat-diet-fed mice. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle, and enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake, resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of WAT de novo lipogenesis gene expression. Thus, reduction in WAT lipolysis reshapes FA fluxes without increase of fat mass and improves glucose metabolism through cell-autonomous induction of fat cell de novo lipogenesis, which contributes to improved insulin sensitivity.

  8. Partial inhibition of adipose tissue lipolysis improves glucose metabolism and insulin sensitivity without alteration of fat mass.

    Science.gov (United States)

    Girousse, Amandine; Tavernier, Geneviève; Valle, Carine; Moro, Cedric; Mejhert, Niklas; Dinel, Anne-Laure; Houssier, Marianne; Roussel, Balbine; Besse-Patin, Aurèle; Combes, Marion; Mir, Lucile; Monbrun, Laurent; Bézaire, Véronic; Prunet-Marcassus, Bénédicte; Waget, Aurélie; Vila, Isabelle; Caspar-Bauguil, Sylvie; Louche, Katie; Marques, Marie-Adeline; Mairal, Aline; Renoud, Marie-Laure; Galitzky, Jean; Holm, Cecilia; Mouisel, Etienne; Thalamas, Claire; Viguerie, Nathalie; Sulpice, Thierry; Burcelin, Rémy; Arner, Peter; Langin, Dominique

    2013-01-01

    When energy is needed, white adipose tissue (WAT) provides fatty acids (FAs) for use in peripheral tissues via stimulation of fat cell lipolysis. FAs have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL) participates in the breakdown of WAT triacylglycerol into FAs. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight, fat mass, and WAT inflammation in high-fat-diet-fed mice. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle, and enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake, resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of WAT de novo lipogenesis gene expression. Thus, reduction in WAT lipolysis reshapes FA fluxes without increase of fat mass and improves glucose metabolism through cell-autonomous induction of fat cell de novo lipogenesis, which contributes to improved insulin sensitivity.

  9. Multiple metabolic alterations exist in mutant PI3K cancers, but only glucose is essential as a nutrient source.

    Directory of Open Access Journals (Sweden)

    Rebecca Foster

    Full Text Available Targeting tumour metabolism is becoming a major new area of pharmaceutical endeavour. Consequently, a systematic search to define whether there are specific energy source dependencies in tumours, and how these might be dictated by upstream driving genetic mutations, is required. The PI3K-AKT-mTOR signalling pathway has a seminal role in regulating diverse cellular processes including cell proliferation and survival, but has also been associated with metabolic dysregulation. In this study, we sought to define how mutations within PI3KCA may affect the metabolic dependency of a cancer cell, using precisely engineered isogenic cell lines. Studies revealed gene expression signatures in PIK3CA mutant cells indicative of a consistent up-regulation of glycolysis. Interestingly, the genes up- and down-regulated varied between isogenic models suggesting that the primary node of regulation is not the same between models. Additional gene expression changes were also observed, suggesting that metabolic pathways other than glycolysis, such as glutaminolysis, were also affected. Nutrient dependency studies revealed that growth of PIK3CA mutant cells is highly dependent on glucose, whereas glutamine dependency is independent of PIK3CA status. In addition, the glucose dependency exhibited by PIK3CA mutant cells could not be overridden by supplementation with other nutrients. This specific dependence on glucose for growth was further illustrated by studies evaluating the effects of targeted disruption of the glycolytic pathway using siRNA and was also found to be present across a wider panel of cancer cell lines harbouring endogenous PIK3CA mutations. In conclusion, we have found that PIK3CA mutations lead to a shift towards a highly glycolytic phenotype, and that despite suggestions that cancer cells are adept at utilising alternative nutrient sources, PIK3CA mutant cells are not able to compensate for glucose withdrawal. Understanding the metabolic

  10. Dietary Salba (Salvia hispanica L) improves the altered metabolic fate of glucose and reduces increased collagen deposition in the heart of insulin-resistant rats.

    Science.gov (United States)

    Creus, Agustina; Benmelej, Adriana; Villafañe, Noelia; Lombardo, Yolanda B

    2017-06-01

    This study reports the effects of dietary Salba (chia) seeds on the mechanisms underlying impaired glucose metabolism in the heart of dyslipemic insulin-resistant rats fed a sucrose-rich diet (SRD). Wistar rats were fed a SRD for 3 months. Afterwards, half the animals continued with the SRD; in the other half's diet chia seeds replaced corn oil (CO) for three months (SRD+chia). In the control group, corn starch replaced sucrose. The replacement of CO by chia seeds in the SRD restored the activities of key enzymes involved in heart glucose metabolism decreasing fatty acid oxidation. Chia seeds normalized insulin stimulated GLUT-4 transporter, the abundance of IRS-1 and pAMPK, changed the profile of fatty acid phospholipids, reduced left-ventricle collagen deposition and normalized hypertension and dyslipidemia. New evidence is provided concerning the effects of dietary chia seeds in improving the altered metabolic fate of glucose in the heart of dyslipemic insulin-resistant rats. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Long-term exposure to abnormal glucose levels alters drug metabolism pathways and insulin sensitivity in primary human hepatocytes

    Science.gov (United States)

    Davidson, Matthew D.; Ballinger, Kimberly R.; Khetani, Salman R.

    2016-06-01

    Hyperglycemia in type 2 diabetes mellitus has been linked to non-alcoholic fatty liver disease, which can progress to inflammation, fibrosis/cirrhosis, and hepatocellular carcinoma. Understanding how chronic hyperglycemia affects primary human hepatocytes (PHHs) can facilitate the development of therapeutics for these diseases. Conversely, elucidating the effects of hypoglycemia on PHHs may provide insights into how the liver adapts to fasting, adverse diabetes drug reactions, and cancer. In contrast to declining PHH monocultures, micropatterned co-cultures (MPCCs) of PHHs and 3T3-J2 murine embryonic fibroblasts maintain insulin-sensitive glucose metabolism for several weeks. Here, we exposed MPCCs to hypo-, normo- and hyperglycemic culture media for ~3 weeks. While albumin and urea secretion were not affected by glucose level, hypoglycemic MPCCs upregulated CYP3A4 enzyme activity as compared to other glycemic states. In contrast, hyperglycemic MPCCs displayed significant hepatic lipid accumulation in the presence of insulin, while also showing decreased sensitivity to insulin-mediated inhibition of glucose output relative to a normoglycemic control. In conclusion, we show for the first time that PHHs exposed to hypo- and hyperglycemia can remain highly functional, but display increased CYP3A4 activity and selective insulin resistance, respectively. In the future, MPCCs under glycemic states can aid in novel drug discovery and mechanistic investigations.

  12. Reduced glucose-induced insulin secretion in low-protein-fed rats is associated with altered pancreatic islets redox status.

    Science.gov (United States)

    Cappelli, Ana Paula G; Zoppi, Claudio C; Silveira, Leonardo R; Batista, Thiago M; Paula, Flávia M; da Silva, Priscilla M R; Rafacho, Alex; Barbosa-Sampaio, Helena C; Boschero, Antonio C; Carneiro, Everardo M

    2018-01-01

    In the present study, we investigated the relationship between early life protein malnutrition-induced redox imbalance, and reduced glucose-stimulated insulin secretion. After weaning, male Wistar rats were submitted to a normal-protein-diet (17%-protein, NP) or to a low-protein-diet (6%-protein, LP) for 60 days. Pancreatic islets were isolated and hydrogen peroxide (H 2 O 2 ), oxidized (GSSG) and reduced (GSH) glutathione content, CuZn-superoxide dismutase (SOD1), glutathione peroxidase (GPx1) and catalase (CAT) gene expression, as well as enzymatic antioxidant activities were quantified. Islets that were pre-incubated with H 2 O 2 and/or N-acetylcysteine, were subsequently incubated with glucose for insulin secretion measurement. Protein malnutrition increased CAT mRNA content by 100%. LP group SOD1 and CAT activities were 50% increased and reduced, respectively. H 2 O 2 production was more than 50% increased whereas GSH/GSSG ratio was near 60% lower in LP group. Insulin secretion was, in most conditions, approximately 50% lower in LP rat islets. When islets were pre-incubated with H 2 O 2 (100 μM), and incubated with glucose (33 mM), LP rats showed significant decrease of insulin secretion. This effect was attenuated when LP islets were exposed to N-acetylcysteine. © 2017 Wiley Periodicals, Inc.

  13. Co-utilization of glucose and xylose by evolved Thermus thermophilus LC113 strain elucidated by (13)C metabolic flux analysis and whole genome sequencing.

    Science.gov (United States)

    Cordova, Lauren T; Lu, Jing; Cipolla, Robert M; Sandoval, Nicholas R; Long, Christopher P; Antoniewicz, Maciek R

    2016-09-01

    We evolved Thermus thermophilus to efficiently co-utilize glucose and xylose, the two most abundant sugars in lignocellulosic biomass, at high temperatures without carbon catabolite repression. To generate the strain, T. thermophilus HB8 was first evolved on glucose to improve its growth characteristics, followed by evolution on xylose. The resulting strain, T. thermophilus LC113, was characterized in growth studies, by whole genome sequencing, and (13)C-metabolic flux analysis ((13)C-MFA) with [1,6-(13)C]glucose, [5-(13)C]xylose, and [1,6-(13)C]glucose+[5-(13)C]xylose as isotopic tracers. Compared to the starting strain, the evolved strain had an increased growth rate (~2-fold), increased biomass yield, increased tolerance to high temperatures up to 90°C, and gained the ability to grow on xylose in minimal medium. At the optimal growth temperature of 81°C, the maximum growth rate on glucose and xylose was 0.44 and 0.46h(-1), respectively. In medium containing glucose and xylose the strain efficiently co-utilized the two sugars. (13)C-MFA results provided insights into the metabolism of T. thermophilus LC113 that allows efficient co-utilization of glucose and xylose. Specifically, (13)C-MFA revealed that metabolic fluxes in the upper part of metabolism adjust flexibly to sugar availability, while fluxes in the lower part of metabolism remain relatively constant. Whole genome sequence analysis revealed two large structural changes that can help explain the physiology of the evolved strain: a duplication of a chromosome region that contains many sugar transporters, and a 5x multiplication of a region on the pVV8 plasmid that contains xylose isomerase and xylulokinase genes, the first two enzymes of xylose catabolism. Taken together, (13)C-MFA and genome sequence analysis provided complementary insights into the physiology of the evolved strain. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  14. Alteration of JNK-1 signaling in skeletal muscle fails to affect glucose homeostasis and obesity-associated insulin resistance in mice.

    Science.gov (United States)

    Pal, Martin; Wunderlich, Claudia M; Spohn, Gabriele; Brönneke, Hella S; Schmidt-Supprian, Marc; Wunderlich, F Thomas

    2013-01-01

    Obesity and associated metabolic disturbances, such as increased circulating fatty acids cause prolonged low grade activation of inflammatory signaling pathways in liver, skeletal muscle, adipose tissue and even in the CNS. Activation of inflammatory pathways in turn impairs insulin signaling, ultimately leading to obesity-associated type 2 diabetes mellitus. Conventional JNK-1 knock out mice are protected from high fat diet-induced insulin resistance, characterizing JNK-1-inhibition as a potential approach to improve glucose metabolism in obese patients. However, the cell type-specific role of elevated JNK-1 signaling as present during the course of obesity has not been fully elucidated yet. To investigate the functional contribution of altered JNK-1 activation in skeletal muscle, we have generated a ROSA26 insertion mouse strain allowing for Cre-activatable expression of a JNK-1 constitutive active construct (JNK(C)). To examine the consequence of skeletal muscle-restricted JNK-1 overactivation in the development of insulin resistance and glucose metabolism, JNK(C) mice were crossed to Mck-Cre mice yielding JNK(SM-C) mice. However, despite increased muscle-specific JNK activation, energy homeostasis and glucose metabolism in JNK(SM-C) mice remained largely unaltered compared to controls. In line with these findings, obese mice with skeletal muscle specific disruption of JNK-1, did not affect energy and glucose homeostasis. These experiments indicate that JNK-1 activation in skeletal muscle does not account for the major effects on diet-induced, JNK-1-mediated deterioration of insulin action and points towards a so far underappreciated role of JNK-1 in other tissues than skeletal muscle during the development of obesity-associated insulin resistance.

  15. Competitive (AP7) and non-competitive (MK-801) NMDA receptor antagonists differentially alter glucose utilization in rat cortex

    International Nuclear Information System (INIS)

    Clow, D.W.; Lee, S.J.; Hammer, R.P. Jr.

    1991-01-01

    The effects of D,L-2-amino-7-phosphonoheptanoic acid (AP7), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, and MK-801, a non-competitive NMDA receptor antagonist, on regional brain metabolism were studied in unanesthetized, freely moving rats by using the quantitative 14 C2-deoxyglucose autoradiographic procedure. AP7 (338 or 901 mg/kg) produced a dose-dependent decrease of metabolic activity throughout most of the regions studied including sensory, motor, and limbic cortices. In contrast, MK-801 (0.1 or 1.0 mg/kg) resulted in a dose-dependent decrease of metabolic activity in sensory cortices, and an increase in limbic regions such as the hippocampal stratum lacunosum moleculare and entorhinal cortex. MK-801 also produced a biphasic response in agranular motor cortex, whereby the low dose increased while the high dose decreased labeling. In addition, MK-801 produced heterogeneous effects on regional cerebral metabolism in sensory cortices. Metabolic activity decreased in layer IV relative to layer Va following MK-801 treatment in primary somatosensory (SI) and visual (VI) cortices, suggesting a shift in activity from afferent fibers innervating layer IV to those innervating layer Va. MK-801 administration also decreased metabolic activity in granular SI relative to dysgranular SI, and in VI relative to secondary visual cortex (VII), thus providing a relative sparing of activity in dysgranular SI and VII. Thus, the non-competitive NMDA receptor antagonist suppressed activity from extrinsic neocortical sources, enhancing relative intracortical activity and stimulating limbic regions, while the competitive NMDA antagonist depressed metabolic activity in all cortical regions

  16. Competitive (AP7) and non-competitive (MK-801) NMDA receptor antagonists differentially alter glucose utilization in rat cortex

    Energy Technology Data Exchange (ETDEWEB)

    Clow, D.W.; Lee, S.J.; Hammer, R.P. Jr. (Department of Anatomy and Reproductive Biology, School of Medicine, University of Hawaii, Honolulu (USA))

    1991-04-01

    The effects of D,L-2-amino-7-phosphonoheptanoic acid (AP7), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, and MK-801, a non-competitive NMDA receptor antagonist, on regional brain metabolism were studied in unanesthetized, freely moving rats by using the quantitative {sup 14}C2-deoxyglucose autoradiographic procedure. AP7 (338 or 901 mg/kg) produced a dose-dependent decrease of metabolic activity throughout most of the regions studied including sensory, motor, and limbic cortices. In contrast, MK-801 (0.1 or 1.0 mg/kg) resulted in a dose-dependent decrease of metabolic activity in sensory cortices, and an increase in limbic regions such as the hippocampal stratum lacunosum moleculare and entorhinal cortex. MK-801 also produced a biphasic response in agranular motor cortex, whereby the low dose increased while the high dose decreased labeling. In addition, MK-801 produced heterogeneous effects on regional cerebral metabolism in sensory cortices. Metabolic activity decreased in layer IV relative to layer Va following MK-801 treatment in primary somatosensory (SI) and visual (VI) cortices, suggesting a shift in activity from afferent fibers innervating layer IV to those innervating layer Va. MK-801 administration also decreased metabolic activity in granular SI relative to dysgranular SI, and in VI relative to secondary visual cortex (VII), thus providing a relative sparing of activity in dysgranular SI and VII. Thus, the non-competitive NMDA receptor antagonist suppressed activity from extrinsic neocortical sources, enhancing relative intracortical activity and stimulating limbic regions, while the competitive NMDA antagonist depressed metabolic activity in all cortical regions.

  17. 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.

  18. C5a receptor deficiency alters energy utilization and fat storage.

    Directory of Open Access Journals (Sweden)

    Christian Roy

    Full Text Available To investigate the impact of whole body C5a receptor (C5aR deficiency on energy metabolism and fat storage.Male wildtype (WT and C5aR knockout (C5aRKO mice were fed a low fat (CHOW or a high fat high sucrose diet-induced obesity (DIO diet for 14 weeks. Body weight and food intake were measured weekly. Indirect calorimetry, dietary fatload clearance, insulin and glucose tolerance tests were also evaluated. Liver, muscle and adipose tissue mRNA gene expression were measured by RT-PCR.At week one and 12, C5aRKO mice on DIO had increased oxygen consumption. After 12 weeks, although food intake was comparable, C5aRKO mice had lower body weight (-7% CHOW, -12% DIO as well as smaller gonadal (-38% CHOW, -36% DIO and inguinal (-29% CHOW, -30% DIO fat pads than their WT counterparts. Conversely, in WT mice, C5aR was upregulated in DIO vs CHOW diets in gonadal adipose tissue, muscle and liver, while C5L2 mRNA expression was lower in C5aRKO on both diet. Furthermore, blood analysis showed lower plasma triglyceride and non-esterified fatty acid levels in both C5aRKO groups, with faster postprandial triglyceride clearance after a fatload. Additionally, C5aRKO mice showed lower CD36 expression in gonadal and muscle on both diets, while DGAT1 expression was higher in gonadal (CHOW and liver (CHOW and DIO and PPARγ was increased in muscle and liver.These observations point towards a role (either direct or indirect for C5aR in energy expenditure and fat storage, suggesting a dual role for C5aR in metabolism as well as in immunity.

  19. Products of glucose and lactate fermentation, and utilization of amino acids by Clostridium estertheticum subspp. laramiense and estertheticum growing in meat juice medium.

    Science.gov (United States)

    Yang, Xianqin; Gill, Colin O; Balamurugan, Sampathkumar

    2010-07-01

    The type strains of Clostridium estertheticum subsp. laramiense and C. estertheticum subsp. estertheticum both utilized glucose and glycogen when growing in meat juice medium and fermented lactate, but ceased growth when glucose was exhausted. The fermentation products from glucose were butyrate, acetate, and formate; those from lactate were 1-butanol, ethanol, butyrate, and formate. Both organisms utilized several amino acids (not containing sulfur) during their cultivation in meat juice medium and did not produce H(2)S. The optimum and maximum temperatures for growth of C. estertheticum subsp. laramiense were 10 degrees C, and 20 to 22 degrees C, respectively. Those same optimum and maximum temperatures have previously been determined for C. estertheticum subsp. estertheticum. The pH range for growth of the two organisms, 5.5 to 7.5, was also the same. Both organisms were beta-hemolytic and formed subterminal spores. Thus, the organisms did not display the difference in fermentation products, optimum and maximum temperatures, hemolysis, and spore position that were reported to be the differentiating characteristics of the subspecies. The findings indicate that vacuum-packaged meat should be spoiled similarly by the two type strains.

  20. Role of 5′AMP-activated protein kinase in glycogen synthase activity and glucose utilization: insights from patients with McArdle's disease

    Science.gov (United States)

    Nielsen, Jakob N; Wojtaszewski, Jørgen F P; Haller, Ronald G; Hardie, D Grahame; Kemp, Bruce E; Richter, Erik A; Vissing, John

    2002-01-01

    It has been suggested that 5′AMP-activated protein kinase (AMPK) is involved in the regulation of glucose and glycogen metabolism in skeletal muscle. We used patients with chronic high muscle glycogen stores and deficient glycogenolysis (McArdle's disease) as a model to address this issue. Six McArdle patients were compared with control subjects during exercise. Muscle α2AMPK activity increased in McArdle patients (from 1.3 ± 0.2 to 1.9 ± 0.2 pmol min−1 mg−1, P = 0.05) but not in control subjects (from 1.0 ± 0.1 to 1.3 ± 0.3 pmol min−1 mg−1). Exercise-induced phosphorylation of the in vivo AMPK substrate acetyl CoA carboxylase (ACCβ; Ser221) was higher (P < 0.01) in McArdle patients than in control subjects (18 ± 3 vs. 10 ± 1 arbitrary units). Exercise-induced whole-body glucose utilization was also higher in McArdle patients than in control subjects (P < 0.05). No correlation between individual AMPK or ACCβ values and glucose utilization was observed. Glycogen synthase (GS) activity was decreased in McArdle patients from 11 ± 1.3 to 5 ± 1.2 % (P < 0.05) and increased in control subjects from 19 ± 1.6 to 23 ± 2.3 % (P < 0.05) in response to exercise. This was not associated with activity changes of GS kinase 3 or protein phosphatase 1, but the changes in GS activity could be due to changes in activity of AMPK or protein kinase A (PKA) as a negative correlation between either ACCβ phosphorylation (Ser221) or plasma adrenaline and GS activity was observed. These findings suggest that GS activity is increased by glycogen breakdown and decreased by AMPK and possibly PKA activation and that the resultant GS activity depends on the relative strengths of the various stimuli. Furthermore, AMPK may be involved in the regulation of glucose utilization during exercise in humans, although the lack of correlation between individual AMPK activity or ACCβ phosphorylation (Ser221) values and individual glucose utilization during exercise implies that AMPK

  1. Type 2 diabetes alters metabolic and transcriptional signatures of glucose and amino acid metabolism during exercise and recovery.

    Science.gov (United States)

    Hansen, Jakob S; Zhao, Xinjie; Irmler, Martin; Liu, Xinyu; Hoene, Miriam; Scheler, Mika; Li, Yanjie; Beckers, Johannes; Hrabĕ de Angelis, Martin; Häring, Hans-Ulrich; Pedersen, Bente K; Lehmann, Rainer; Xu, Guowang; Plomgaard, Peter; Weigert, Cora

    2015-08-01

    The therapeutic benefit of physical activity to prevent and treat type 2 diabetes is commonly accepted. However, the impact of the disease on the acute metabolic response is less clear. To this end, we investigated the effect of type 2 diabetes on exercise-induced plasma metabolite changes and the muscular transcriptional response using a complementary metabolomics/transcriptomics approach. We analysed 139 plasma metabolites and hormones at nine time points, and whole genome expression in skeletal muscle at three time points, during a 60 min bicycle ergometer exercise and a 180 min recovery phase in type 2 diabetic patients and healthy controls matched for age, percentage body fat and maximal oxygen consumption (VO2). Pathway analysis of differentially regulated genes upon exercise revealed upregulation of regulators of GLUT4 (SLC2A4RG, FLOT1, EXOC7, RAB13, RABGAP1 and CBLB), glycolysis (HK2, PFKFB1, PFKFB3, PFKM, FBP2 and LDHA) and insulin signal mediators in diabetic participants compared with controls. Notably, diabetic participants had normalised rates of lactate and insulin levels, and of glucose appearance and disappearance, after exercise. They also showed an exercise-induced compensatory regulation of genes involved in biosynthesis and metabolism of amino acids (PSPH, GATM, NOS1 and GLDC), which responded to differences in the amino acid profile (consistently lower plasma levels of glycine, cysteine and arginine). Markers of fat oxidation (acylcarnitines) and lipolysis (glycerol) did not indicate impaired metabolic flexibility during exercise in diabetic participants. Type 2 diabetic individuals showed specific exercise-regulated gene expression. These data provide novel insight into potential mechanisms to ameliorate the disturbed glucose and amino acid metabolism associated with type 2 diabetes.

  2. Impact of overexpressing NADH kinase on glucose and xylose metabolism in recombinant xylose-utilizing Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Hou, Jin; Vemuri, G. N.; Bao, X. M.

    2009-01-01

    of overexpressing the native NADH kinase (encoded by the POS5 gene) in xylose-consuming recombinant S. cerevisiae directed either into the cytosol or to the mitochondria was evaluated. The physiology of the NADH kinase containing strains was also evaluated during growth on glucose. Overexpressing NADH kinase...

  3. Differences in lateral hemispheric asymmetries of glucose utilization between early- and late-onset Alzheimer-type dementia

    Energy Technology Data Exchange (ETDEWEB)

    Koss, E.; Friedland, R.P.; Ober, B.A.; Jagust, W.J.

    1985-05-01

    Positron emission tomography with (/sup 18/F)fluorodeoxyglucose revealed greater right than left hemispheric impairment of cortical glucose metabolism in patients with probable Alzheimer's disease who were younger than 65 but not in those over 65. This asymmetry was related to poor visuospatial performance.

  4. Neuronal Cell Death Induced by Mechanical Percussion Trauma in Cultured Neurons is not Preceded by Alterations in Glucose, Lactate and Glutamine Metabolism

    DEFF Research Database (Denmark)

    Jayakumar, A R; Bak, L K; Rama Rao, K V

    2016-01-01

    to neurobehavioral and cognitive impairments, that usually develop months to years after single or repetitive episodes of head trauma, are major consequences of chronic TBI. The molecular mechanisms responsible for TBI-induced injury, however, are unclear. Recent studies have suggested that early mitochondrial......Traumatic brain injury (TBI) is a devastating neurological disorder that usually presents in acute and chronic forms. Brain edema and associated increased intracranial pressure in the early phase following TBI are major consequences of acute trauma. On the other hand, neuronal injury, leading...... dysfunction and subsequent energy failure play a role in the pathogenesis of TBI. We therefore examined whether oxidative metabolism of (13)C-labeled glucose, lactate or glutamine is altered early following in vitro mechanical percussion-induced trauma (5 atm) to neurons (4-24 h), and whether such events...

  5. Long-term testosterone treatment during pregnancy does not alter insulin or glucose profile in a sheep model of polycystic ovary syndrome.

    Science.gov (United States)

    Recabarren, Monica; Carrasco, Albert; Sandoval, Daniel; Diaz, Felipe; Sir-Petermann, Teresa; Recabarren, Sergio E

    2017-09-07

    The administration of testosterone to pregnant sheep to resemble fetal programming of the polycystic ovary syndrome could alter other hormones/factors of maternal origin with known effects on fetal growth. Hence, we studied the weekly profile of insulin, progesterone and glucose during a treatment with testosterone propionate given biweekly from weeks 5 to 17 of pregnancy (term at 21 weeks) and checked the outcome of their fetuses at 17 weeks of gestation after C-section. Control dams were only exposed to the vehicle of the hormone. The testosterone administration did not cause any significant change in the maternal weekly profile of insulin, progesterone or glucose concentration, although the plasma levels of testosterone in the treated dams were inversely correlated to the levels of progesterone. Testosterone treatment also induced an inverse correlation between mean maternal insulin levels and fetal insulin levels; however, the fetal zoometric parameters, body weight, or insulin levels did not differ between exposed and not exposed fetuses. Therefore, treatment with testosterone during pregnancy does not cause significant impact on insulin levels in the mother, leading to less effect on the programming of fetal growth.

  6. 6-Paradol and 6-Shogaol, the Pungent Compounds of Ginger, Promote Glucose Utilization in Adipocytes and Myotubes, and 6-Paradol Reduces Blood Glucose in High-Fat Diet-Fed Mice

    Directory of Open Access Journals (Sweden)

    Chien-Kei Wei

    2017-01-01

    Full Text Available The anti-diabetic activity of ginger powder (Zingiber officinale has been recently promoted, with the recommendation to be included as one of the dietary supplements for diabetic patients. However, previous studies presented different results, which may be caused by degradation and metabolic changes of ginger components, gingerols, shogaols and paradols. Therefore, we prepared 10 ginger active components, namely 6-, 8-, 10-paradols, 6-, 8-, 10-shogaols, 6-, 8-, 10-gingerols and zingerone, and evaluated their anti-hyperglycemic activity. Among the tested compounds, 6-paradol and 6-shogaol showed potent activity in stimulating glucose utilization by 3T3-L1 adipocytes and C2C12 myotubes. The effects were attributed to the increase in 5′ adenosine monophosphate-activated protein kinase (AMPK phosphorylation in 3T3-L1 adipocytes. 6-Paradol, the major metabolite of 6-shogaol, was utilized in an in vivo assay and significantly reduced blood glucose, cholesterol and body weight in high-fat diet-fed mice.

  7. Prenatal Exposure to Sodium Arsenite Alters Placental Glucose 1, 3, and 4 Transporters in Balb/c Mice

    Science.gov (United States)

    Gutiérrez-Torres, Daniela Sarahí; González-Horta, Carmen; Del Razo, Luz María; Infante-Ramírez, Rocío; Ramos-Martínez, Ernesto; Levario-Carrillo, Margarita; Sánchez-Ramírez, Blanca

    2015-01-01

    Inorganic arsenic (iAs) exposure induces a decrease in glucose type 4 transporter (GLUT4) expression on the adipocyte membrane, which may be related to premature births and low birth weight infants in women exposed to iAs at reproductive age. The aim of this study was to analyze the effect of sodium arsenite (NaAsO2) exposure on GLUT1, GLUT3, and GLUT4 protein expression and on placental morphology. Female Balb/c mice (n = 15) were exposed to 0, 12, and 20 ppm of NaAsO2 in drinking water from 8th to 18th day of gestation. Morphological changes and GLUT1, GLUT3, and GLUT4 expression were evaluated in placentas by immunohistochemical and image analysis and correlated with iAs and arsenical species concentration, which were quantified by atomic absorption spectroscopy. NaAsO2 exposure induced a significant decrease in fetal and placental weight (P < 0.01) and increases in infarctions and vascular congestion. Whereas GLUT1 expression was unchanged in placentas from exposed group, GLUT3 expression was found increased. In contrast, GLUT4 expression was significantly lower (P < 0.05) in placentas from females exposed to 12 ppm. The decrease in placental GLUT4 expression might affect the provision of adequate fetal nutrition and explain the low fetal weight observed in the exposed groups. PMID:26339590

  8. Prenatal Exposure to Sodium Arsenite Alters Placental Glucose 1, 3, and 4 Transporters in Balb/c Mice

    Directory of Open Access Journals (Sweden)

    Daniela Sarahí Gutiérrez-Torres

    2015-01-01

    Full Text Available Inorganic arsenic (iAs exposure induces a decrease in glucose type 4 transporter (GLUT4 expression on the adipocyte membrane, which may be related to premature births and low birth weight infants in women exposed to iAs at reproductive age. The aim of this study was to analyze the effect of sodium arsenite (NaAsO2 exposure on GLUT1, GLUT3, and GLUT4 protein expression and on placental morphology. Female Balb/c mice (n=15 were exposed to 0, 12, and 20 ppm of NaAsO2 in drinking water from 8th to 18th day of gestation. Morphological changes and GLUT1, GLUT3, and GLUT4 expression were evaluated in placentas by immunohistochemical and image analysis and correlated with iAs and arsenical species concentration, which were quantified by atomic absorption spectroscopy. NaAsO2 exposure induced a significant decrease in fetal and placental weight (P<0.01 and increases in infarctions and vascular congestion. Whereas GLUT1 expression was unchanged in placentas from exposed group, GLUT3 expression was found increased. In contrast, GLUT4 expression was significantly lower (P<0.05 in placentas from females exposed to 12 ppm. The decrease in placental GLUT4 expression might affect the provision of adequate fetal nutrition and explain the low fetal weight observed in the exposed groups.

  9. Simultaneous measurement of local glucose utilization and blood flow in the rat brain: an autoradiographic method using two tracers labeled with carbon-14

    International Nuclear Information System (INIS)

    Furlow, T.W. Jr.; Martin, R.M.; Harrison, L.E.

    1983-01-01

    A simplified technique that uses two radionuclide tracers has been devised to measure local cerebral glucose utilization (ICGU) and local cerebral blood flow (ICBF) in the same rat. The method employs [ 14 C]-2-deoxyglucose and [ 14 C]iodoantipyrine to produce an autoradiogram before and another after extraction into chloroform of the [ 14 C]iodoantipyrine from the brain sections. The chloroform-extracted autoradiogram yields ICGU, and the difference in tissue carbon-14 concentration between the two autoradiograms permits calculation of ICBF. The double-isotope technique provides values of ICGU and ICBF that are statistically indistinguishable from those derived from conventional single-isotope methods

  10. Glucose is required to maintain high ATP-levels for the energy utilizing steps during PDT-induced apoptosis

    International Nuclear Information System (INIS)

    Oberdanner, C.; Plaetzer, K.; Kiesslich, T.; Krammer, B.

    2003-01-01

    Full text: Photodynamic therapy (PDT) may trigger apoptosis or necrosis in cancer cells. Several steps in the induction and execution of apoptosis require high amounts of adenosine-5'-triphosphate (ATP). Since the mitochondrial membrane potential (ΔΨ) decreases early in apoptosis, we raised the question about the mechanisms of maintaining a sufficiently high ATP-level. We therefore monitored ΔΨ and the intracellular ATP-level of apoptotic human epidermoid carcinoma cells (A431) after photodynamic treatment with aluminium (III) phthalocyanine tetrasulfonate chloride. A maximum of caspase-3 activation and nuclear fragmentation was found at fluences of about 4 J.cm -2 . Under these conditions apoptotic cells reduced ΔΨ rapidly, while the ATP-level remained high for 4 to 6 hours after treatment for cells supplied with glucose. To analyze the contribution of glycolysis to the energy supply during apoptosis experiments were carried out with cells deprivated of glucose. These cells showed a rapid drop of ATP-content and neither caspase-activation nor nuclear fragmentation could be detected. We conclude that the use of glucose as a source of ATP is obligatory for the execution of PDT-induced apoptosis. (author)

  11. Altered TNF-Alpha, Glucose, Insulin and Amino Acids in Islets Langerhans Cultured in a Microgravity Model System

    Science.gov (United States)

    Tobin, Brian W.; Leeper-Woodford, Sandra K.; Hashemi, Brian B.; Smith, Scott M.; Sams, Clarence F.

    2001-01-01

    The present studies were designed to determine effects of a microgravity model system upon lipopolysaccharide (LPS) stimulated tumor necrosis factor alpha (TNF-alpha) activity and indices of insulin and fuel homeostasis of pancreatic islets of Langerhans. Islets (1726+/-1 17,150 u IEU) from Wistar Furth rats were treated as: 1) HARV (High Aspect Ratio Vessel cell culture) , 2) HARV plus LPS, 3) static culture, 4) static culture plus LPS. TNF-alpha (L929 cytotoxicity assay) was significantly increased in LPS-induced HARV and static cultures, yet the increase was more pronounced in the static culture group (pinsulin concentration was demonstrated in the LPS stimulated HARV culture (palterations in LPS induced TNF-alpha production of pancreatic islets of Langerhans, favoring a lesser TNF activity in the HARV. These alterations in fuel homeostasis may be promulgated by gravity averaged cell culture methods or by three dimensional cell assembly.

  12. Eucommia bark (Du-Zhong improves diabetic nephropathy without altering blood glucose in type 1-like diabetic rats

    Directory of Open Access Journals (Sweden)

    Niu HS

    2016-03-01

    Full Text Available Ho-Shan Niu,1 I-Min Liu,2 Chiang-Shan Niu,1 Po-Ming Ku,3,4 Chao-Tien Hsu,5 Juei-Tang Cheng4,6 1Department of Nursing, Tzu Chi University of Science and Technology, Hualien City, 2Department of Pharmacy & Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung County, 3Department of Cardiology, 4Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, 5Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung City, 6Institute of Medical Science, College of Health Science, Chang Jung Christian University, Guei-Ren, Tainan City, Taiwan Background: Eucommia bark, Eucommia ulmoides Oliver barks (Du-Zhong in Mandarin, is an herb used for renal dysfunction in Chinese traditional medicine. In an attempt to develop this herb as a treatment for diabetic nephropathy (DN, we investigated the effects of Du-Zhong on renal dysfunction in type 1-like diabetic rats. Methods: Streptozotocin (STZ was used to induce type 1-like diabetes in rats (STZ-diabetic rats. In addition to hyperglycemia, STZ-diabetic rats showed significant nephropathy, including higher plasma levels of blood urea nitrogen, creatinine, and renal fibrosis. Western blot analysis of renal cortical tissue was applied to characterize the changes in potential signals related to nephropathy. Results: Oral administration of Du-Zhong (1 g/kg/day to STZ-diabetic rats for 20 days not only decreased the plasma levels of blood urea nitrogen and creatinine but also improved renal fibrosis, whereas the plasma glucose level was not changed. The higher expressions of protein levels of transforming growth factor-beta (TGF-β and connective tissue growth factor in diabetic rats were markedly attenuated by Du-Zhong. The increased phosphorylation of Smad2/3 in STZ-diabetic rats was also reduced by Du-Zhong. However, Du-Zhong cannot reverse the hyperglycemia-induced overproduction of signal transducers and activators of transcription 3 in the diabetic kidney

  13. Glucose utilization in the brain during acute seizure is a useful biomarker for the evaluation of anticonvulsants: effect of methyl ethyl ketone in lithium-pilocarpine status epilepticus rats

    International Nuclear Information System (INIS)

    Yamada, Akifumi; Momosaki, Sotaro; Hosoi, Rie; Abe, Kohji; Yamaguchi, Masatoshi; Inoue, Osamu

    2009-01-01

    Enhancement of glucose utilization in the brain has been well known during acute seizure in various kinds of animal model of epilepsy. This enhancement of glucose utilization might be related to neural damage in these animal models. Recently, we found that methyl ethyl ketone (MEK) had both anticonvulsive and neuroprotective effects in lithium-pilocapine (Li-pilo) status epilepticus (SE) rat. In this article, we measured the uptake of [ 14 C]2-deoxyglucose ([ 14 C]DG) in the Li-pilo SE and Li-pilo SE with MEK rat brain in order to assess whether the glucose utilization was a useful biomarker for the detection of efficacy of anticonvulsive compounds. Significant increase of [ 14 C]DG uptake (45 min after the injection) in the cerebral cortex, hippocampus, amygdala and thalamus during acute seizure induced by Li-pilo were observed. On the other hand, the initial uptake of [ 14 C]DG (1 min after the injection) in the Li-pilo SE rats was not different from the control rats. Therefore, the enhancement of glucose metabolism during acute seizure was due to the facilitation of the rate of phosphorylation process of [ 14 C]DG in the brain. Pretreatment with MEK (8 mmol/kg) completely abolished the enhancement of glucose utilization in the Li-pilo SE rats. The present results indicated that glucose utilization in the brain during acute seizure might be a useful biomarker for the evaluation of efficacy of anticonvulsive compounds.

  14. Glucose utilization in the brain during acute seizure is a useful biomarker for the evaluation of anticonvulsants: effect of methyl ethyl ketone in lithium-pilocarpine status epilepticus rats

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Akifumi [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan)], E-mail: yamaaki@sahs.med.osaka-u.ac.jp; Momosaki, Sotaro; Hosoi, Rie [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan); Abe, Kohji [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan); Developmental Research Laboratories, Shionogi and Co., Ltd., Toyonaka, Osaka, 561-0825 (Japan); Yamaguchi, Masatoshi [Faculty of Pharmaceutical Sciences, Fukuoka University, Johnan, Fukuoka 814-0180 (Japan); Inoue, Osamu [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan)

    2009-11-15

    Enhancement of glucose utilization in the brain has been well known during acute seizure in various kinds of animal model of epilepsy. This enhancement of glucose utilization might be related to neural damage in these animal models. Recently, we found that methyl ethyl ketone (MEK) had both anticonvulsive and neuroprotective effects in lithium-pilocapine (Li-pilo) status epilepticus (SE) rat. In this article, we measured the uptake of [{sup 14}C]2-deoxyglucose ([{sup 14}C]DG) in the Li-pilo SE and Li-pilo SE with MEK rat brain in order to assess whether the glucose utilization was a useful biomarker for the detection of efficacy of anticonvulsive compounds. Significant increase of [{sup 14}C]DG uptake (45 min after the injection) in the cerebral cortex, hippocampus, amygdala and thalamus during acute seizure induced by Li-pilo were observed. On the other hand, the initial uptake of [{sup 14}C]DG (1 min after the injection) in the Li-pilo SE rats was not different from the control rats. Therefore, the enhancement of glucose metabolism during acute seizure was due to the facilitation of the rate of phosphorylation process of [{sup 14}C]DG in the brain. Pretreatment with MEK (8 mmol/kg) completely abolished the enhancement of glucose utilization in the Li-pilo SE rats. The present results indicated that glucose utilization in the brain during acute seizure might be a useful biomarker for the evaluation of efficacy of anticonvulsive compounds.

  15. Blood flow, flow reserve, and glucose utilization in viable and nonviable myocardium in patients with ischemic cardiomyopathy.

    Science.gov (United States)

    Zhang, Xiaoli; Schindler, Thomas H; Prior, John O; Sayre, James; Dahlbom, Magnus; Huang, Sung-Cheng; Schelbert, Heinrich R

    2013-04-01

    The aim of the study was to determine whether glucose uptake in viable myocardium of ischemic cardiomyopathy patients depends on rest myocardial blood flow (MBF) and the residual myocardial flow reserve (MFR). Thirty-six patients with ischemic cardiomyopathy (left ventricular ejection fraction 25 ± 10 %) were studied with (13)N-ammonia and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Twenty age-matched normals served as controls. Regional MBF was determined at rest and during dipyridamole hyperemia and regional FDG extraction was estimated from regional FDG to (13)N-ammonia activity ratios. Rest MBF was reduced in viable (0.42 ± 0.18 ml/min per g) and nonviable regions (0.32 ± 0.09 ml/min per g) relative to remote regions (0.68 ± 0.23 ml/min per g, p MFRs did not differ significantly (p > 0.05). Compared to MFR in remote myocardium, MFRs in viable regions were similar (1.39 ± 0.56 vs 1.70 ± 0.45, p > 0.05) but were significantly lower in nonviable regions (1.23 ± 0.43, p MFRs (r =-0.424, p MFRs in viable myocardium are associated with increasing glucose extraction that likely reflects a metabolic adaptation of remodeling hibernating myocytes.

  16. TNFα altered inflammatory responses, impaired health and productivity, but did not affect glucose or lipid metabolism in early-lactation dairy cows.

    Directory of Open Access Journals (Sweden)

    Kai Yuan

    Full Text Available Inflammation may be a major contributing factor to peripartum metabolic disorders in dairy cattle. We tested whether administering an inflammatory cytokine, recombinant bovine tumor necrosis factor-α (rbTNFα, affects milk production, metabolism, and health during this period. Thirty-three Holstein cows (9 primiparous and 24 multiparous were randomly assigned to 1 of 3 treatments at parturition. Treatments were 0 (Control, 1.5, or 3.0 µg/kg body weight rbTNFα, which were administered once daily by subcutaneous injection for the first 7 days of lactation. Statistical contrasts were used to evaluate the treatment and dose effects of rbTNFα administration. Plasma TNFα concentrations at 16 h post-administration tended to be increased (P0.10 was detected; rbTNFα treatments increased (P0.10 by rbTNFα administration, but 6 out of 16 measured eicosanoids changed (P0.10 by rbTNFα treatment. Glucose turnover rate was unaffected (P=0.18 by rbTNFα administration. The higher dose of rbTNFα tended to increase the risk of cows developing one or more health disorders (P=0.08. Taken together, these results indicate that administration of rbTNFα daily for the first 7 days of lactation altered inflammatory responses, impaired milk production and health, but did not significantly affect liver triglyceride accumulation or nutrient metabolism in dairy cows.

  17. Substrate specificity of glucose dehydrogenase and carbon source utilization pattern of pantoea dispersa strain P2 and its radiation induced mutants

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young Keun; Murugesan, Senthilkumar [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

    2009-06-15

    Mineral phosphate solubilizing pantoea dispersa strain P2 produced 5.5 mM and 42.6 mM of gluconic acid on 24 h and 72 h incubation, respectively. Strain P2 exhibited glucose dehydrogenase (GDH) specific activity of 0.32 IU mg{sup -1} protein. We have studied the substrate specificity of GDH as well as carbon source utilization pattern of strain P2. GDH of strain P2 did not use ribose as substrate. Utilization of lactose with specific activity of 0.65 IU mg{sup -1} protein indicated that the enzyme belongs to GDH type B isozyme. Arabinose, galactose, ribose, sucrose and xylose did not induce the synthesis of GDH enzyme while mannose induced the synthesis of GDH with highest specific activity of 0.58 IU mg{sup -1} protein. Through radiation mutagenesis, the substrate specificity of GDH was modified in order to utilize side range of sugars available in root exudates. Ribose, originally not a substrate for GDH of strain P2 was utilized as substrate by mutants P2-M5 with specific activity of 0.44 and 0.57 IU mg{sup -1} protein, respectively. Specific activity of GDH on the media containing lactose and galactose was also improved to 1.2 and 0.52 IU mg{sup -1} protein in P2-M5 and P2-M6 respectively. Based on the carbon source availability in root exudate, the mutants can be selected and utilized as efficient biofertilizer under P-deficient soil conditions.

  18. Substrate specificity of glucose dehydrogenase and carbon source utilization pattern of pantoea dispersa strain P2 and its radiation induced mutants

    International Nuclear Information System (INIS)

    Lee, Young Keun; Murugesan, Senthilkumar

    2009-01-01

    Mineral phosphate solubilizing pantoea dispersa strain P2 produced 5.5 mM and 42.6 mM of gluconic acid on 24 h and 72 h incubation, respectively. Strain P2 exhibited glucose dehydrogenase (GDH) specific activity of 0.32 IU mg -1 protein. We have studied the substrate specificity of GDH as well as carbon source utilization pattern of strain P2. GDH of strain P2 did not use ribose as substrate. Utilization of lactose with specific activity of 0.65 IU mg -1 protein indicated that the enzyme belongs to GDH type B isozyme. Arabinose, galactose, ribose, sucrose and xylose did not induce the synthesis of GDH enzyme while mannose induced the synthesis of GDH with highest specific activity of 0.58 IU mg -1 protein. Through radiation mutagenesis, the substrate specificity of GDH was modified in order to utilize side range of sugars available in root exudates. Ribose, originally not a substrate for GDH of strain P2 was utilized as substrate by mutants P2-M5 with specific activity of 0.44 and 0.57 IU mg -1 protein, respectively. Specific activity of GDH on the media containing lactose and galactose was also improved to 1.2 and 0.52 IU mg -1 protein in P2-M5 and P2-M6 respectively. Based on the carbon source availability in root exudate, the mutants can be selected and utilized as efficient biofertilizer under P-deficient soil conditions

  19. 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

  20. Studies of gene expression and activity of hexokinase, phosphofructokinase and glycogen synthase in human skeletal muscle in states of altered insulin-stimulated glucose metabolism

    DEFF Research Database (Denmark)

    Vestergaard, H

    1999-01-01

    When whole body insulin-stimulated glucose disposal rate is measured in man applying the euglycaemic, hyperinsulinaemic clamp technique it has been shown that approximately 75% of glucose is taken up by skeletal muscle. After the initial transport step, glucose is rapidly phosphorylated to glucose...... due to an increased glycogen synthesis rate in muscle, which is paralleled by an increased total GS activity, increased GS mRNA levels and enhanced insulin-stimulated activation of GS. These changes are probably due to local contraction-dependent mechanisms. Likewise, one-legged exercise training has...

  1. Rapid Response: To Scan or Not to Scan? The Utility of Noncontrast CT Head for Altered Mental Status.

    Science.gov (United States)

    Thacker, Purujit J; Sethi, Mansha; Sternlieb, Jonathan; Schneider, Doron; Naglak, Mary; Patel, Rajeshkumar R

    2018-01-17

    The aims of the study were the following: (1) to determine how often computed tomography (CT) scans of the head are obtained on rapid responses called for altered mental status (AMS), (2) to determine whether CT imaging of the head is required during all rapid responses called for AMS, (3) to determine which patients would benefit from CT scans of the head in this setting, (4) to note whether an adequate neurologic exam was documented, (5) to determine the cost of CT scans that did not change management, and (6) to examine the role of medications leading to AMS. The study was a retrospective chart review at Abington Jefferson Hospital. Data collected included the age, sex, time of rapid response, clinical condition of the patient, whether an arterial blood gas and blood glucose were done, and whether a neurological exam was documented in the resident's rapid response team note. The patient's medications were also reviewed. Computed tomography scan findings as well as changes made in a patient's care as a result of the scan were recorded. Any findings that did not lead to a change in management were considered a "negative" scan. Overall, 610 rapid responses were activated from January to August 2016. One hundred four (17.04%) of the total rapid responses were for AMS and 83 (79.8%) of these patients underwent noncontrast CT scan of the head. The mean (SD) age of the patients was 74.7 (13.6) years. A total of 56.6% were female. The most frequent clinical conditions documented at the time of rapid responses were noted as confused (33.7%, 28/83), either lethargic or unconscious (32.5%, 27/83), and concern for stroke (21.7%, 18/83). A total of 96.4% (80/83) of the CT scans done were negative for any acute changes. The three patients with positive scans (3/83) had a change in management as a result of the scans. If patients with symptoms concerning for stroke and unconscious patients are excluded, the total number of remaining patients is 56. Of these, zero patients had

  2. Abnormalities of glucose metabolism in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Gouveia L.M.F.B.

    2000-01-01

    Full Text Available Abnormalities in glucose metabolism and insulin action are frequently detected in patients with essential hypertension. Spontaneously hypertensive rats (SHR have been used as an experimental model to understand this pathological condition. The objective of the present study was to assess glucose metabolism and insulin action in SHR and Wistar rats under fed and fasting conditions. Peripheral glucose utilization was estimated by kinetic studies with [6-³H]-glucose and gluconeogenetic activity was measured during continuous [14C]-bicarbonate infusion. Plasma glucose levels were higher in the SHR group. Plasma insulin levels in the fed state were higher in the SHR group (99.8 ± 6.5 µM than in the control group (70.4 ± 3.6 µM. Muscle glycogen content was reduced in SHR compared to control under the various experimental conditions. Peripheral glucose utilization was slightly lower in the SHR group in the fed state (8.72 ± 0.55 vs 9.52 ± 0.80 mg kg-1 min-1 in controls. Serum free fatty acid levels, hepatic glycogen levels, hepatic phosphoenolpyruvate carboxykinase activity and gluconeogenetic activity were similar in the two groups. The presence of hyperglycemia and hyperinsulinemia and the slightly reduced peripheral glucose utilization suggest the presence of resistance to the action of insulin in peripheral tissues of SHR. Hepatic gluconeogenesis does not seem to contribute to the metabolic alterations detected in these animals.

  3. The Effects of Insulin and Glucose on Different Characteristics of a UPEC: Alterations in Growth Rate and Expression Levels of some Virulence Genes.

    Science.gov (United States)

    Gumus, Defne; Yoruk, Emre; Kalayci-Yuksek, Fatma; Uz, Gulsen; Topal-Sarikaya, Aysegul; Ang-Kucuker, Mine

    2017-10-01

    Host factors are known to modulate virulence, antibiotic susceptibility, and growth rate of bacteria. The effect of human insulin and glucose on growth rate and expression of virulence genes (usp, sfa/foc, cnf1) of a uropathogenic E. coli (UPEC) strain were investigated in this study. E. coli C7 was grown in tryptic soy broth (TSB-control) and TSB containing 20 µU/mL insulin, 200 µU/mL insulin, 0.1% glucose, and 200 µU/mL insulin + 0.1% glucose. Growth rates were determined via optical density measurement in a spectrophotometer. Real-time polymerase chain reaction was used to determine the gene expression levels. Statistical analyses were performed via Tukey's post hoc-test. Differences were found to be not statistically significant for bacterial growth rate in TSB and TSB with insulin and/or glucose. The expression levels of all three virulence genes were shown to be reduced significantly in the presence of insulin and/or glucose. The highest degree of repression was observed in 200 µU/mL insulin added to TSB. Also, the repression level of the gene expression was revealed to be reduced in 0.1% glucose supplemented TSB. In the present study, it was shown that insulin and glucose can modulate UPEC's gene expression while the growth rate was not affected.

  4. Altered substrate utilization caused by respiratory uncoupling in white fat of P2-Ucp1 transgenic mice

    Czech Academy of Sciences Publication Activity Database

    Rossmeisl, Martin; Janovská, Petra; Kůs, Vladimír; Matějčková, Eva; Kopecký, Jan

    2005-01-01

    Roč. 48, Suppl.1 (2005), A204-A205 ISSN 0012-186X. [EASD Annual meting /41./. 10.09.2005-15.09.2005, Athens] R&D Projects: GA ČR GA303/03/0749; GA ČR GA303/05/2580 Institutional research plan: CEZ:AV0Z50110509 Keywords : transgenic mice * obesity * mitochondria * glucose tolerance * indirect calorimetry Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition

  5. Alterations in Energy/Redox Metabolism Induced by Mitochondrial and Environmental Toxins: A Specific Role for Glucose-6-Phosphate-Dehydrogenase and the Pentose Phosphate Pathway in Paraquat Toxicity

    Science.gov (United States)

    2015-01-01

    Parkinson’s disease (PD) is a multifactorial disorder with a complex etiology including genetic risk factors, environmental exposures, and aging. While energy failure and oxidative stress have largely been associated with the loss of dopaminergic cells in PD and the toxicity induced by mitochondrial/environmental toxins, very little is known regarding the alterations in energy metabolism associated with mitochondrial dysfunction and their causative role in cell death progression. In this study, we investigated the alterations in the energy/redox-metabolome in dopaminergic cells exposed to environmental/mitochondrial toxins (paraquat, rotenone, 1-methyl-4-phenylpyridinium [MPP+], and 6-hydroxydopamine [6-OHDA]) in order to identify common and/or different mechanisms of toxicity. A combined metabolomics approach using nuclear magnetic resonance (NMR) and direct-infusion electrospray ionization mass spectrometry (DI-ESI-MS) was used to identify unique metabolic profile changes in response to these neurotoxins. Paraquat exposure induced the most profound alterations in the pentose phosphate pathway (PPP) metabolome. 13C-glucose flux analysis corroborated that PPP metabolites such as glucose-6-phosphate, fructose-6-phosphate, glucono-1,5-lactone, and erythrose-4-phosphate were increased by paraquat treatment, which was paralleled by inhibition of glycolysis and the TCA cycle. Proteomic analysis also found an increase in the expression of glucose-6-phosphate dehydrogenase (G6PD), which supplies reducing equivalents by regenerating nicotinamide adenine dinucleotide phosphate (NADPH) levels. Overexpression of G6PD selectively increased paraquat toxicity, while its inhibition with 6-aminonicotinamide inhibited paraquat-induced oxidative stress and cell death. These results suggest that paraquat “hijacks” the PPP to increase NADPH reducing equivalents and stimulate paraquat redox cycling, oxidative stress, and cell death. Our study clearly demonstrates that alterations

  6. Formerly obese, now thin and confused: the utility of mnemonics in the approach to altered mental status.

    Science.gov (United States)

    Burski, Chad M; Miller, Chad S; Centor, Robert M

    2013-12-01

    Altered mental status represents a common cause for admission to general medicine services. Often a significant workup ensues to define an underlying etiology. When a history of bariatric surgery with small bowel resection precedes the presentation, the differential diagnosis expands. We review a patient, having prior bariatric surgery and small bowel resection, who presents with altered mental status. After an extensive workup, she was diagnosed with a rare clinical problem, D-lactic acidosis. In presenting this case, we examine the use of mnemonics in medicine and how this can assist in solving clinical problems.

  7. Altered energy state reversibly controls smooth muscle contractile function in human saphenous vein during acute hypoxia-reoxygenation: Role of glycogen, AMP-activated protein kinase, and insulin-independent glucose uptake.

    Science.gov (United States)

    Pyla, Rajkumar; Pichavaram, Prahalathan; Fairaq, Arwa; Park, Mary Anne; Kozak, Mark; Kamath, Vinayak; Patel, Vijay S; Segar, Lakshman

    2015-09-01

    Hypoxia is known to promote vasodilation of coronary vessels through several mediators including cardiac-derived adenosine and endothelium-derived prostanoids and nitric oxide. To date, the impact of endogenous glycogen depletion in vascular smooth muscle and the resultant alterations in cellular energy state (e.g., AMP-activated protein kinase, AMPK) on the contractile response to G protein-coupled receptor agonists (e.g., serotonin, 5-HT) has not yet been studied. In the present study, ex vivo exposure of endothelium-denuded human saphenous vein rings to hypoxic and glucose-deprived conditions during KCl-induced contractions for 30 min resulted in a marked depletion of endogenous glycogen by ∼80% (from ∼1.78 μmol/g under normoxia to ∼0.36 μmol/g under hypoxia). Importantly, glycogen-depleted HSV rings, which were maintained under hypoxia/reoxygenation and glucose-deprived conditions, exhibited significant increases in basal AMPK phosphorylation (∼6-fold ↑) and 5-HT-induced AMPK phosphorylation (∼19-fold ↑) with an accompanying suppression of 5-HT-induced maximal contractile response (∼68% ↓), compared with respective controls. Exposure of glycogen-depleted HSV rings to exogenous D-glucose, but not the inactive glucose analogs, prevented the exaggerated increase in 5-HT-induced AMPK phosphorylation and restored 5-HT-induced maximal contractile response. In addition, the ability of exogenous D-glucose to rescue cellular stress and impaired contractile function occurred through GLUT1-mediated but insulin/GLUT4-independent mechanisms. Together, the present findings from clinically-relevant human saphenous vein suggest that the loss of endogenous glycogen in vascular smooth muscle and the resultant accentuation of AMPK phosphorylation by GPCR agonists may constitute a yet another mechanism of metabolic vasodilation of coronary vessels in ischemic heart disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Change in hexose distribution volume and fractional utilization of [18F]-2-deoxy-2-fluoro-D-glucose in brain during acute hypoglycemia in humans

    International Nuclear Information System (INIS)

    Shapiro, E.T.; Cooper, M.; Chen, C.T.; Given, B.D.; Polonsky, K.S.

    1990-01-01

    We used positron emission tomography (PET) to study the effects of mild hypoglycemia on cerebral glucose uptake and metabolism. Nine healthy men were studied under basal saline-infusion conditions, and during euglycemic and hypoglycemic clamp studies. Insulin was infused at the same rate (1 mU.kg-1.min-1) in both clamp studies. In euglycemic clamp studies, glucose was infused at a rate sufficient to maintain the basal plasma glucose concentration, whereas in hypoglycemic clamp studies, the glucose infusion rate was reduced to maintain the plasma glucose at 3.1 mM. Each study lasted 3 h and included a 30-min baseline period and a subsequent 150-min period in which insulin or glucose was administered. Blood samples for measurement of insulin, glucose, cortisol, growth hormone, and glucagon were obtained at 20- to 30-min intervals. A bolus injection of 5-10 mCi [18F]-2-deoxy-2-fluoro-D-glucose (2-DFG) was administered 120 min after initiation of the study, and plasma radioactivity and dynamic PET scans were obtained at frequent intervals for the remaining 40-60 min of the study. Cerebral regions of interest were defined, and concentrations of radioactivity were calculated and used in the three-compartment model of 2-DFG distribution described by Sokoloff. Glucose levels were similar during saline-infusion (4.9 +/- 0.1 mM) and euglycemic clamp (4.8 +/- 0.1 mM) studies, whereas the desired degree of mild hypoglycemia was achieved during the hypoglycemic clamp study (3.1 +/- 0.1 mM, P less than 0.05). The insulin level during saline infusion was 41 +/- 7 pM

  9. Growth Hormone Receptor Antagonist Transgenic Mice Have Increased Subcutaneous Adipose Tissue Mass, Altered Glucose Homeostasis and No Change in White Adipose Tissue Cellular Senescence.

    Science.gov (United States)

    Comisford, Ross; Lubbers, Ellen R; Householder, Lara A; Suer, Ozan; Tchkonia, Tamara; Kirkland, James L; List, Edward O; Kopchick, John J; Berryman, Darlene E

    2016-01-01

    Growth hormone (GH)-resistant/deficient mice experience improved glucose homeostasis and substantially increased lifespan. Recent evidence suggests that long-lived GH-resistant/deficient mice are protected from white adipose tissue (WAT) dysfunction, including WAT cellular senescence, impaired adipogenesis and loss of subcutaneous WAT in old age. This preservation of WAT function has been suggested to be a potential mechanism for the extended lifespan of these mice. The objective of this study was to examine WAT senescence, WAT distribution and glucose homeostasis in dwarf GH receptor antagonist (GHA) transgenic mice, a unique mouse strain having decreased GH action but normal longevity. 18-month-old female GHA mice and wild-type (WT) littermate controls were used. Prior to dissection, body composition, fasting blood glucose as well as glucose and insulin tolerance tests were performed. WAT distribution was determined by weighing four distinct WAT depots at the time of dissection. Cellular senescence in four WAT depots was assessed using senescence-associated β-galactosidase staining to quantify the senescent cell burden, and real-time qPCR to quantify gene expression of senescence markers p16 and IL-6. GHA mice had a 22% reduction in total body weight, a 33% reduction in lean mass and a 10% increase in body fat percentage compared to WT controls. GHA mice had normal fasting blood glucose and improved insulin sensitivity; however, they exhibited impaired glucose tolerance. Moreover, GHA mice displayed enhanced lipid storage in the inguinal subcutaneous WAT depot (p < 0.05) and a 1.7-fold increase in extra-/intraperitoneal WAT ratio compared to controls (p < 0.05). Measurements of WAT cellular senescence showed no difference between GHA mice and WT controls. Similar to other mice with decreased GH action, female GHA mice display reduced age-related lipid redistribution and improved insulin sensitivity, but no change in cellular senescence. The similar abundance of

  10. Growth hormone receptor antagonist (GHA) transgenic mice have increased subcutaneous adipose tissue mass, altered glucose homeostasis, and no change in white adipose tissue cellular senescence

    Science.gov (United States)

    Comisford, Ross; Lubbers, Ellen R.; Householder, Lara; Suer, Ozan; Tchkonia, Tamara; Kirkland, James L.; List, Edward O.; Kopchick, John J.; Berryman, Darlene E.

    2015-01-01

    Background Growth hormone (GH) resistant/deficient mice experience improved glucose homeostasis and substantially increased lifespan. Recent evidence suggests long-lived GH resistant/deficient mice are protected from white adipose tissue (WAT) dysfunction, including WAT cellular senescence, impaired adipogenesis and loss of subcutaneous WAT in old age. This preservation of WAT function has been suggested to be a potential mechanism for the extended lifespan of these mice. OBJECTIVE The objective of this study was to examine white adipose tissue (WAT) senescence, WAT distribution, and glucose homeostasis in dwarf growth hormone receptor antagonist (GHA) transgenic mice, a unique mouse strain having decreased GH action but normal longevity. METHODS 18mo old female GHA mice and wild type (WT) littermate controls were used. Prior to dissection, body composition, fasting blood glucose, and glucose and insulin tolerance tests were performed. WAT distribution was determined by weighing four distinct WAT depots at the time of dissection. Cellular senescence in four WAT depots was assessed using senescence-associated β-galactosidase (SA-β-gal) staining to quantify the senescent cell burden and real time qPCR to quantify gene expression of senescence markers p16 and IL-6. RESULTS GHA mice had a 22% reduction in total body weight, 33% reduction in lean mass, and a 10% increase in body fat percentage compared to WT controls. GHA mice had normal fasting blood glucose and improved insulin sensitivity; however, they exhibited impaired glucose tolerance. Moreover, GHA mice displayed enhanced lipid storage in the inguinal subcutaneous WAT depot (p<.05) and a 1.7 fold increase in extra-/intraperitoneal WAT ratio compared to controls (p<.05). Measurements of WAT cellular senescence showed no difference between GHA mice and WT controls. CONCLUSIONS Similar to other mice with decreased GH action, female GHA mice display reduced age-related lipid redistribution and improved insulin

  11. Effect of a Health Care System Respiratory Fluoroquinolone Restriction Program To Alter Utilization and Impact Rates of Clostridium difficile Infection.

    Science.gov (United States)

    Shea, Katherine M; Hobbs, Athena L V; Jaso, Theresa C; Bissett, Jack D; Cruz, Christopher M; Douglass, Elizabeth T; Garey, Kevin W

    2017-06-01

    Fluoroquinolones are one of the most commonly prescribed antibiotic classes in the United States despite their association with adverse consequences, including Clostridium difficile infection (CDI). We sought to evaluate the impact of a health care system antimicrobial stewardship-initiated respiratory fluoroquinolone restriction program on utilization, appropriateness of quinolone-based therapy based on institutional guidelines, and CDI rates. After implementation, respiratory fluoroquinolone utilization decreased from a monthly mean and standard deviation (SD) of 41.0 (SD = 4.4) days of therapy (DOT) per 1,000 patient days (PD) preintervention to 21.5 (SD = 6.4) DOT/1,000 PD and 4.8 (SD = 3.6) DOT/1,000 PD posteducation and postrestriction, respectively. Using segmented regression analysis, both education (14.5 DOT/1,000 PD per month decrease; P = 0.023) and restriction (24.5 DOT/1,000 PD per month decrease; P respiratory fluoroquinolone use occurred postrestriction versus preintervention in patients administered at least one dose (74/130 [57%] versus 74/232 [32%]; P respiratory fluoroquinolone, was observed postrestriction compared to preintervention within the health care system ($123,882 versus $12,273; P = 0.002). Implementation of a stewardship-initiated respiratory fluoroquinolone restriction program can increase appropriate use while reducing overall utilization, acquisition cost, and CDI rates within a health care system. Copyright © 2017 American Society for Microbiology.

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

    Science.gov (United States)

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

    2016-06-01

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

  13. Momordica charantia ameliorates insulin resistance and dyslipidemia with altered hepatic glucose production and fatty acid synthesis and AMPK phosphorylation in high-fat-fed mice.

    Science.gov (United States)

    Shih, Chun-Ching; Shlau, Min-Tzong; Lin, Cheng-Hsiu; Wu, Jin-Bin

    2014-03-01

    Momordica charantia Linn. (Cucurbitaceae) fruit is commonly known as bitter melon. C57BL/6J mice were firstly divided randomly into two groups: the control (CON) group was fed with a low-fat diet, whereas the experimental group was fed a 45% high-fat (HF) diet for 8 weeks. Afterwards, the CON group was treated with vehicle, whereas the HF group was subdivided into five groups and still on HF diet and was given orally M. charantia extract (MCE) or rosiglitazone (Rosi) or not for 4 weeks. M. charantia decreased the weights of visceral fat and caused glucose lowering. AMP-activated protein kinase (AMPK) is a major cellular regulator of lipid and glucose metabolism. MCE significantly increases the hepatic protein contents of AMPK phosphorylation by 126.2-297.3% and reduces expression of phosphenolpyruvate carboxykinase (PEPCK) and glucose production. Most importantly, MCE decreased expression of hepatic 11beta hydroxysteroid dehydroxygenase (11beta-HSD1) gene, which contributed in attenuating diabetic state. Furthermore, MCE lowered serum triglycerides (TGs) by inhibition of hepatic fatty acid synthesis by dampening sterol response element binding protein 1c and fatty acid synthase mRNA leading to reduction in TGs synthesis. This study demonstrates M. charantia ameliorates diabetic and hyperlipidemic state in HF-fed mice occurred by regulation of hepatic PEPCK, 11beta-HSD1 and AMPK phosphorylation. Copyright © 2013 John Wiley & Sons, Ltd.

  14. The rs340874 PROX1 type 2 diabetes mellitus risk variant is associated with visceral fat accumulation and alterations in postprandial glucose and lipid metabolism.

    Science.gov (United States)

    Kretowski, Adam; Adamska, Edyta; Maliszewska, Katarzyna; Wawrusiewicz-Kurylonek, Natalia; Citko, Anna; Goscik, Joanna; Bauer, Witold; Wilk, Juliusz; Golonko, Anna; Waszczeniuk, Magdalena; Lipinska, Danuta; Hryniewicka, Justyna; Niemira, Magdalena; Paczkowska, Magdalena; Ciborowski, Michal; Gorska, Maria

    2015-03-01

    Large-scale meta-analyses of genome-wide association studies have recently confirmed that the rs340874 single-nucleotide polymorphism in PROX1 gene is associated with fasting glycemia and type 2 diabetes mellitus; however, the mechanism of this link was not well established. The aim of our study was to evaluate the functional/phenotypic differences related to rs340874 PROX1 variants. The study group comprised 945 subjects of Polish origin (including 634 with BMI > 25) without previously known dysglycemia. We analyzed behavioral patterns (diet, physical activity), body fat distribution and glucose/fat metabolism after standardized meals and during the oral glucose tolerance test. We found that the carriers of the rs340874 PROX1 CC genotype had higher nonesterified fatty acids levels after high-fat meal (p = 0.035) and lower glucose oxidation (p = 0.014) after high-carbohydrate meal in comparison with subjects with other PROX1 genotypes. Moreover, in subjects with CC variant, we found higher accumulation of visceral fat (p food consumption (p diabetes mellitus. The study may help to understand the mechanisms of visceral obesity and type 2 diabetes mellitus risk development.

  15. Glucose Sensing

    CERN Document Server

    Geddes, Chris D

    2006-01-01

    Topics in Fluorescence Spectroscopy, Glucose Sensing is the eleventh volume in the popular series Topics in Fluorescence Spectroscopy, edited by Drs. Chris D. Geddes and Joseph R. Lakowicz. This volume incorporates authoritative analytical fluorescence-based glucose sensing reviews specialized enough to be attractive to professional researchers, yet also appealing to the wider audience of scientists in related disciplines of fluorescence. Glucose Sensing is an essential reference for any lab working in the analytical fluorescence glucose sensing field. All academics, bench scientists, and industry professionals wishing to take advantage of the latest and greatest in the continuously emerging field of glucose sensing, and diabetes care & management, will find this volume an invaluable resource. Topics in Fluorescence Spectroscopy Volume 11, Glucose Sensing Chapters include: Implantable Sensors for Interstitial Fluid Smart Tattoo Glucose Sensors Optical Enzyme-based Glucose Biosensors Plasmonic Glucose Sens...

  16. Altered insulin receptor messenger ribonucleic acid splicing in liver is associated with deterioration of glucose tolerance in the spontaneously obese and diabetic rhesus monkey: Analysis of controversy between monkey and human studies

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Ze; Shuldiner, A.R.; Zenilman, M.E. [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States)] [and others

    1996-04-01

    There are two insulin receptor (IR) isoforms (designated type A and type B), derived from alternative splicing of exon 11 of the IR gene. Recently, we reported that an increase in the exon 11- (i.e. lacking exon 11) (type A) IR messenger RNA (mRNA) variant in muscle is associated with hyperinsulinemia, an early risk factor for noninsulin-dependent diabetes mellitus (NIDDM), in the spontaneously obese, diabetic rhesus monkey. To explore further the role of IR mRNA splicing in insulin resistance of NIDDM, we studied liver, another target organ that is resistant to insulin action in NIDDM. The relative amounts of the two IR mRNA-splicing variants in liver were quantitated by RT-PCR in normal, prediabetic, and diabetic (NIDDM) monkeys. The percentage of the exon 11- mRNA variant in liver (n = 24) was significantly correlated with fasting plasma glucose (r = 0.55, P < 0.01) and intravenous glucose disappearance rate (r = -0.45, P < 0.05). The exon 11- mRNA variant was increased significantly from 29.8 {+-} 1.6% in monkeys with normal fasting glucose to 39.2 {+-} 2.9% in monkeys with elevated fasting glucose (P < 0.01). These studies provide the first direct evidence in vivo that the relative expression of the two IR mRNA-splicing variants is altered in liver and suggest that increased expression of the exon 11- IR isoform may contribute to hepatic insulin resistance and NIDDM or may compensate for some yet unidentified defect. 33 refs., 3 figs., 1 tab.

  17. [Utility of immunohistochemistry in detecting alterations of mismatch repair genes of DNA. A series of 48 cases of colorectal cancer].

    Science.gov (United States)

    Ziadi, Sonia; Gacem, Riath Ben; Haoues, Imen; Hachana, Mouhamed; Amara, Khaled; Trimeche, Mounir; Golli, Lamia; Mokni, Moncef; Korbi, Sadok

    2011-01-01

    Hereditary non-polyposis colorectal cancer (HNPCC) is associated in more than 95% to a germline mutation in the genes of the mismatch repair (MMR) of DNA. The aim of this study was to assess the utility of immunohistochemistry, a simple and fast technique, in the triage of families where HNPCC is suspected. Tumor samples included in this study were from patients with resection for colorectal cancer, examined in our laboratory between 2004 and 2007. For each case, a formalin-fixed paraffin-embedded tissue block containing tumor tissue and normal adjacent mucosa was selected. Tumor specimens were examined with immunohistochemistry for the presence of hMLH1, hMSH2, and hMSH6 proteins. Scoring of the tumor staining was performed without any knowledge of patients' family history. The loss of protein expression was noted in four patients among 48 cases tested: two cases with isolated loss of hMSH2, a case with isolated loss of hMSH6 and one case with combined loss of MSH2/MSH6. No case has shown a suppression of hMLH1 protein. Comparing the immunohistochemical results for clinical has revealed a clear correlation between loss of protein expression demonstrated by immunohistochemistry and clinical data. Indeed, three cases among the four who showed no expression of MMR proteins showed at least one clinical criterion predictive of HNPCC. In conclusion, our study support the potential utility of immunohistochemistry to identify a significant portion of colorectal tumors derived from germline mutation of MMR genes and can be used as an adjunct measure in the identification of HNPCC.

  18. A systematic approach for the accurate non-invasive estimation of blood glucose utilizing a novel light-tissue interaction adaptive modelling scheme

    Energy Technology Data Exchange (ETDEWEB)

    Rybynok, V O; Kyriacou, P A [City University, London (United Kingdom)

    2007-10-15

    Diabetes is one of the biggest health challenges of the 21st century. The obesity epidemic, sedentary lifestyles and an ageing population mean prevalence of the condition is currently doubling every generation. Diabetes is associated with serious chronic ill health, disability and premature mortality. Long-term complications including heart disease, stroke, blindness, kidney disease and amputations, make the greatest contribution to the costs of diabetes care. Many of these long-term effects could be avoided with earlier, more effective monitoring and treatment. Currently, blood glucose can only be monitored through the use of invasive techniques. To date there is no widely accepted and readily available non-invasive monitoring technique to measure blood glucose despite the many attempts. This paper challenges one of the most difficult non-invasive monitoring techniques, that of blood glucose, and proposes a new novel approach that will enable the accurate, and calibration free estimation of glucose concentration in blood. This approach is based on spectroscopic techniques and a new adaptive modelling scheme. The theoretical implementation and the effectiveness of the adaptive modelling scheme for this application has been described and a detailed mathematical evaluation has been employed to prove that such a scheme has the capability of extracting accurately the concentration of glucose from a complex biological media.

  19. A systematic approach for the accurate non-invasive estimation of blood glucose utilizing a novel light-tissue interaction adaptive modelling scheme

    Science.gov (United States)

    Rybynok, V. O.; Kyriacou, P. A.

    2007-10-01

    Diabetes is one of the biggest health challenges of the 21st century. The obesity epidemic, sedentary lifestyles and an ageing population mean prevalence of the condition is currently doubling every generation. Diabetes is associated with serious chronic ill health, disability and premature mortality. Long-term complications including heart disease, stroke, blindness, kidney disease and amputations, make the greatest contribution to the costs of diabetes care. Many of these long-term effects could be avoided with earlier, more effective monitoring and treatment. Currently, blood glucose can only be monitored through the use of invasive techniques. To date there is no widely accepted and readily available non-invasive monitoring technique to measure blood glucose despite the many attempts. This paper challenges one of the most difficult non-invasive monitoring techniques, that of blood glucose, and proposes a new novel approach that will enable the accurate, and calibration free estimation of glucose concentration in blood. This approach is based on spectroscopic techniques and a new adaptive modelling scheme. The theoretical implementation and the effectiveness of the adaptive modelling scheme for this application has been described and a detailed mathematical evaluation has been employed to prove that such a scheme has the capability of extracting accurately the concentration of glucose from a complex biological media.

  20. A systematic approach for the accurate non-invasive estimation of blood glucose utilizing a novel light-tissue interaction adaptive modelling scheme

    International Nuclear Information System (INIS)

    Rybynok, V O; Kyriacou, P A

    2007-01-01

    Diabetes is one of the biggest health challenges of the 21st century. The obesity epidemic, sedentary lifestyles and an ageing population mean prevalence of the condition is currently doubling every generation. Diabetes is associated with serious chronic ill health, disability and premature mortality. Long-term complications including heart disease, stroke, blindness, kidney disease and amputations, make the greatest contribution to the costs of diabetes care. Many of these long-term effects could be avoided with earlier, more effective monitoring and treatment. Currently, blood glucose can only be monitored through the use of invasive techniques. To date there is no widely accepted and readily available non-invasive monitoring technique to measure blood glucose despite the many attempts. This paper challenges one of the most difficult non-invasive monitoring techniques, that of blood glucose, and proposes a new novel approach that will enable the accurate, and calibration free estimation of glucose concentration in blood. This approach is based on spectroscopic techniques and a new adaptive modelling scheme. The theoretical implementation and the effectiveness of the adaptive modelling scheme for this application has been described and a detailed mathematical evaluation has been employed to prove that such a scheme has the capability of extracting accurately the concentration of glucose from a complex biological media

  1. Exposure to bisphenol-A during pregnancy partially mimics the effects of a high-fat diet altering glucose homeostasis and gene expression in adult male mice.

    Directory of Open Access Journals (Sweden)

    Marta García-Arevalo

    Full Text Available Bisphenol-A (BPA is one of the most widespread EDCs used as a base compound in the manufacture of polycarbonate plastics. The aim of our research has been to study how the exposure to BPA during pregnancy affects weight, glucose homeostasis, pancreatic β-cell function and gene expression in the major peripheral organs that control energy flux: white adipose tissue (WAT, the liver and skeletal muscle, in male offspring 17 and 28 weeks old. Pregnant mice were treated with a subcutaneous injection of 10 µg/kg/day of BPA or a vehicle from day 9 to 16 of pregnancy. One month old offspring were divided into four different groups: vehicle treated mice that ate a normal chow diet (Control group; BPA treated mice that also ate a normal chow diet (BPA; vehicle treated animals that had a high fat diet (HFD and BPA treated animals that were fed HFD (HFD-BPA. The BPA group started to gain weight at 18 weeks old and caught up to the HFD group before week 28. The BPA group as well as the HFD and HFD-BPA ones presented fasting hyperglycemia, glucose intolerance and high levels of non-esterified fatty acids (NEFA in plasma compared with the Control one. Glucose stimulated insulin release was disrupted, particularly in the HFD-BPA group. In WAT, the mRNA expression of the genes involved in fatty acid metabolism, Srebpc1, Pparα and Cpt1β was decreased by BPA to the same extent as with the HFD treatment. BPA treatment upregulated Pparγ and Prkaa1 genes in the liver; yet it diminished the expression of Cd36. Hepatic triglyceride levels were increased in all groups compared to control. In conclusion, male offspring from BPA-treated mothers presented symptoms of diabesity. This term refers to a form of diabetes which typically develops in later life and is associated with obesity.

  2. Exposure to Bisphenol-A during Pregnancy Partially Mimics the Effects of a High-Fat Diet Altering Glucose Homeostasis and Gene Expression in Adult Male Mice

    Science.gov (United States)

    García-Arevalo, Marta; Alonso-Magdalena, Paloma; Rebelo Dos Santos, Junia; Quesada, Ivan; Carneiro, Everardo M.; Nadal, Angel

    2014-01-01

    Bisphenol-A (BPA) is one of the most widespread EDCs used as a base compound in the manufacture of polycarbonate plastics. The aim of our research has been to study how the exposure to BPA during pregnancy affects weight, glucose homeostasis, pancreatic β-cell function and gene expression in the major peripheral organs that control energy flux: white adipose tissue (WAT), the liver and skeletal muscle, in male offspring 17 and 28 weeks old. Pregnant mice were treated with a subcutaneous injection of 10 µg/kg/day of BPA or a vehicle from day 9 to 16 of pregnancy. One month old offspring were divided into four different groups: vehicle treated mice that ate a normal chow diet (Control group); BPA treated mice that also ate a normal chow diet (BPA); vehicle treated animals that had a high fat diet (HFD) and BPA treated animals that were fed HFD (HFD-BPA). The BPA group started to gain weight at 18 weeks old and caught up to the HFD group before week 28. The BPA group as well as the HFD and HFD-BPA ones presented fasting hyperglycemia, glucose intolerance and high levels of non-esterified fatty acids (NEFA) in plasma compared with the Control one. Glucose stimulated insulin release was disrupted, particularly in the HFD-BPA group. In WAT, the mRNA expression of the genes involved in fatty acid metabolism, Srebpc1, Pparα and Cpt1β was decreased by BPA to the same extent as with the HFD treatment. BPA treatment upregulated Pparγ and Prkaa1 genes in the liver; yet it diminished the expression of Cd36. Hepatic triglyceride levels were increased in all groups compared to control. In conclusion, male offspring from BPA-treated mothers presented symptoms of diabesity. This term refers to a form of diabetes which typically develops in later life and is associated with obesity. PMID:24959901

  3. Glucose metabolism is altered after loss of L cells and α-cells but not influenced by loss of K cells

    DEFF Research Database (Denmark)

    Pedersen, J; Ugleholdt, Randi Kjærsgaard; Jørgensen, Signe Marie

    2013-01-01

    , and glucagon is associated with impaired regulation of metabolism. This study evaluates the consequences of acute removal of Gip- or Gcg-expressing cells on glucose metabolism. Generation of the two diphtheria toxin receptor cellular knockout mice, TgN(GIP.DTR) and TgN(GCG.DTR), allowed us to study effects...... of acute ablation of K and L cells and α-cells. Diphtheria toxin administration reduced the expression of Gip and content of GIP in the proximal jejunum in TgN(GIP.DTR) and expression of Gcg and content of proglucagon-derived peptides in both proximal jejunum and terminal ileum as well as content...

  4. Subjective-Objective Sleep Discrepancy Is Associated With Alterations in Regional Glucose Metabolism in Patients With Insomnia and Good Sleeper Controls.

    Science.gov (United States)

    Kay, Daniel B; Karim, Helmet T; Soehner, Adriane M; Hasler, Brant P; James, Jeffrey A; Germain, Anne; Hall, Martica H; Franzen, Peter L; Price, Julie C; Nofzinger, Eric A; Buysse, Daniel J

    2017-11-01

    Sleep discrepancies are common in primary insomnia (PI) and include reports of longer sleep onset latency (SOL) than measured by polysomnography (PSG) or "negative SOL discrepancy." We hypothesized that negative SOL discrepancy in PI would be associated with higher relative glucose metabolism during nonrapid eye movement (NREM) sleep in brain networks involved in conscious awareness, including the salience, left executive control, and default mode networks. PI (n = 32) and good sleeper controls (GS; n = 30) completed [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans during NREM sleep, and relative regional cerebral metabolic rate for glucose (rCMRglc) was measured. Sleep discrepancy was calculated by subtracting PSG-measured SOL on the PET night from corresponding self-report values the following morning. We tested for interactions between group (PI vs. GS) and SOL discrepancy for rCMRglc during NREM sleep using both a region of interest mask and exploratory whole-brain analyses. Significant group by SOL discrepancy interactions for rCMRglc were observed in several brain regions (pcorrected PSG-measured SOL) was associated with significantly higher relative rCMRglc in the right anterior insula and middle/posterior cingulate during NREM sleep. In GS, more positive SOL discrepancy (self-reported Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  5. Alterations in blood glucose and plasma glucagon concentrations during deep brain stimulation in the shell region of the nucleus accumbens in rats

    NARCIS (Netherlands)

    Diepenbroek, Charlene; van der Plasse, Geoffrey; Eggels, Leslie; Rijnsburger, Merel; Feenstra, Matthijs G. P.; Kalsbeek, Andries; Denys, Damiaan; Fliers, Eric; Serlie, Mireille J.; la Fleur, Susanne E.

    2013-01-01

    Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is an effective therapy for obsessive compulsive disorder (OCD) and is currently under investigation as a treatment for eating disorders. DBS of this area is associated with altered food intake and pharmacological treatment of OCD is

  6. Peroxisome Proliferator-Activated Receptor-alpha-Null Mice Have Increased White Adipose Tissue Glucose Utilization, GLUT4, and Fat Mass: Role in Liver and Brain

    NARCIS (Netherlands)

    Knauf, C.; Rieusset, J.; Foretz, M.; Cani, P.D.; Uldry, M.; Hosokawa, M.; Martinez, E.; Bringart, M.; Waget, A.; Kersten, A.H.; Desvergne, B.; Gremlich, S.; Wahli, W.; Seydoux, J.; Delzenne, N.M.; Thorens, B.; Burcelin, R.

    2006-01-01

    Activation of the peroxisome proliferator-activated receptor (PPAR)-¿ increases lipid catabolism and lowers the concentration of circulating lipid, but its role in the control of glucose metabolism is not as clearly established. Here we compared PPAR¿ knockout mice with wild type and confirmed that

  7. Metabolic flux pattern of glucose utilization by Xanthomonas campestris pv. campestris: prevalent role of the Entner-Doudoroff pathway and minor fluxes through the pentose phosphate pathway and glycolysis.

    Science.gov (United States)

    Schatschneider, Sarah; Huber, Claudia; Neuweger, Heiko; Watt, Tony Francis; Pühler, Alfred; Eisenreich, Wolfgang; Wittmann, Christoph; Niehaus, Karsten; Vorhölter, Frank-Jörg

    2014-10-01

    The well-studied plant pathogenic bacterium Xanthomonas campestris pv. campestris (Xcc) synthesizes the biotechnologically important polysaccharide xanthan gum, which is also regarded as a virulence factor in plant interactions. In Xcc, sugars like glucose are utilized as a source to generate energy and biomass for growth and pathogenicity. In this study, we used [1-(13)C]glucose as a tracer to analyze the fluxes in the central metabolism of the bacterium growing in a minimal medium. (13)C-Metabolic flux analysis based on gas chromatography-mass spectrometry (GC-MS) confirmed the prevalent catabolic role of the Entner-Doudoroff pathway. Comparative nuclear magnetic resonance (NMR)-based isotopologue profiling of a mutant deficient in glycolysis gave evidence for a moderate flux via glycolysis in the wild-type. In addition to reconfirming the Entner-Doudoroff pathway as a catabolic main route, this approach affirmed a numerically minor but important flux via the pentose phosphate pathway.

  8. Comparing Alterations of Blood Glucose Level in type II Diabetic Patients Taking Metformin and Withhold of Metformin on the Morning of Coronary Artery Bypass Graft Surgery

    Directory of Open Access Journals (Sweden)

    M. Tarbiat

    2016-07-01

    Full Text Available Introduction & Objective: In the context effect of metformin in patients with acute coronary syndrome, available evidence supports cardiac effect. Yet, there is doubt about continuation or discontinuation of metformin before major surgery. The aim of the present study is to determine the efficacy of continuing metformin in plasma glucose, renal function index, arterial PH in type II diabetic patients after coronary artery bypass graft surgery. Materials & Methods: In this clinical-experimental study, 90 type II diabetic patients with ASA class II admitted for CABG surgery in Hamadan Ekbatan Hospital were enrolled in the study in 2014 and were randomly assigned to two groups , one group treated with insulin and continued metformin and the other group treated with insulin and discontinued metformin.In the beginning indicators such as age, sex, body mass index (BMI were compared which were not significantly different in the two groups. Then, other parameters such as blood glucose, BUN, Cr, arterial blood PH, cardiac arrhythmia and need for inotrope were compared. Used inotropes in this study included dopamine, dobutamine, epinephrine, norepinephrine, milrinon to achieve systolic blood presser pressure over 100mmHg. Results: Average plasma BUN after surgery and one day after surgery in the group who discontinued metformin significantly were higher compared with the metformin group, but no differences were observed in average plasma BUN in the 2nd and 3rd days after surgery in the two groups. During 3 days after surgery, average plasma creatinine was significantly lower in metformin group compared to non- metformin group. Although there was no difference between the two groups in pH parameter before surgery but in the metformin group, average pH was lower than non-metformin group after surgery. Before and 3 days after surgery mean blood glucose level was not significantly different between the two groups. During surgery, average need for inotrope in

  9. Does Ramadan fasting alter body weight and blood lipids and fasting blood glucose in a healthy population? A meta-analysis.

    Science.gov (United States)

    Kul, Seval; Savaş, Esen; Öztürk, Zeynel Abidin; Karadağ, Gülendam

    2014-06-01

    In this study, we conducted a meta-analysis of self-controlled cohort studies comparing body weights, blood levels of lipids and fasting blood glucose levels before and after Ramadan taking into account gender differences. Several databases were searched up to June 2012 for studies showing an effect of Ramadan fasting in healthy subjects, yielding 30 articles. The primary finding of this meta-analysis was that after Ramadan fasting, low-density lipoprotein (SMD = -1.67, 95 % CI = -2.48 to -0.86) and fasting blood glucose levels (SMD = -1.10, 95 % CI = -1.62 to -0.58) were decreased in both sex groups and also in the entire group compared to levels prior to Ramadan. In addition, in the female subgroup, body weight (SMD = -0.04, 95 % CI = -0.20, 0.12), total cholesterol (SMD = 0.05, 95 % CI = -0.51 to 0.60), and triglyceride levels (SMD = 0.03, 95 % CI = -0.31, 0.36) remained unchanged, while HDL levels (SMD = 0.86, 95 % CI = 0.11 to 1.61, p = 0.03) were increased. In males, Ramadan fasting resulted in weight loss (SMD = -0.24, 95 % CI = -0.36, -0.12, p = 0.001). Also, a substantial reduction in total cholesterol (SMD = -0.44, 95 % CI = -0.77 to -0.11) and LDL levels (SMD = -2.22, 95 % CI = -3.47 to -0.96) and a small decrease in triglyceride levels (SMD = -0.35, 95 % CI = -0.67 to -0.02) were observed in males. In conclusion, by looking at this data, it is evident that Ramadan fasting can effectively change body weight and some biochemical parameters in healthy subjects especially in males compared to pre-Ramadan period.

  10. Sodium Nitrate Induces Reactive Oxygen Species That Lower the Antioxidant Power, Damage the Membrane, and Alter Pathways of Glucose Metabolism in Human Erythrocytes.

    Science.gov (United States)

    Ansari, Fariheen Aisha; Mahmood, Riaz

    2015-12-09

    Nitrate salts are widely used as food additives and nitrogenous fertilizers and are present as contaminants in drinking water supplies. The effect of different concentrations (1-15 mM) of sodium nitrate (NaNO3) on human erythrocytes was studied under in vitro conditions. Treatment of erythrocytes with NaNO3 resulted in increases in methemoglobin levels, lipid peroxidation, and protein oxidation and a decrease in glutathione content. There were changes in the activities of all major antioxidant defense enzymes, and the pathways of glucose metabolism were also affected. Increased generation of reactive oxygen species (ROS) took place while the antioxidant power was impaired. The osmotic fragility of cells was increased, and membrane-bound enzymes were greatly inhibited. All changes were statistically significant at a probability level of P < 0.05 at all concentrations of NaNO3 except the lowest (1 mM). Thus, NaNO3 generates ROS that cause significant damage to human erythrocytes and interfere in normal cellular pathways.

  11. Excessive fluoride consumption increases haematological alteration in subjects with iron deficiency, thalassaemia, and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

    Science.gov (United States)

    Pornprasert, Sakorn; Wanachantararak, Phenphichar; Kantawong, Fahsai; Chamnanprai, Supoj; Kongpan, Chatpat; Pienthai, Nattasit; Yanola, Jintana; Duangmano, Suwit; Prasannarong, Mujalin

    2017-08-01

    Excessive fluoride consumption leads to accelerated red blood cell death and anaemia. Whether that increases the haematological alteration in subjects with haematological disorders (iron deficiency, thalassaemia, and G-6-PD deficiency) is still unclear. The fluoride in serum and urine and haematological parameters of students at Mae Tuen School (fluoride endemic area) were analysed and compared to those of students at Baan Yang Poa and Baan Mai Schools (control areas). Iron deficiency, thalassaemia, and G-6-PD deficiency were also diagnosed in these students. The students at Mae Tuen School had significantly (P fluoride in the serum and urine than those in control areas. In both control and fluoride endemic areas, students with haematological disorders had significantly lower levels of Hb, Hct, MCV, MCH, and MCHC than those without haematological disorders. Moreover, the lowest levels of Hb, MCH, and MCHC were observed in the students with haematological disorders who live in the fluoride endemic area. Thus, the excessive fluoride consumption increased haematological alteration in subjects with iron deficiency, thalassaemia, and G-6-PD deficiency and that may increase the risk of anaemia in these subjects.

  12. Multilevel model based glucose control for type-1 diabetes patients.

    Science.gov (United States)

    Garcia-Gabin, Winston; Jacobsen, Elling W

    2013-01-01

    Diabetes is a disease that involves alterations at multiple biological levels, ranging from intracellular signalling to organ processes. Since glucose homeostasis is the consequence of complex interactions that involve a number of factors, the control of diabetes should be based on a multilevel analysis. In this paper, a novel approach to design of closed-loop glucose controllers based on multilevel models is presented. A control scheme is proposed based on combining a pharmacokinetic/pharmacodynamic model with an insulin signal transduction model for type 1 diabetes mellitus patients. Based on this, an insulin feedback control schemes is designed. Two main advantages of explicitly utilizing information at the intracellular level were obtained. First, significant reduction of hypoglycaemic risk by reducing the undershoot in glucose levels in response to added insulin. Second, robust performance for inter-patient changes, demonstrated through application of the multilevel control strategy to a well established in silico population of diabetic patients.

  13. Comparison of serum glucose and salivary glucose in diabetic patients

    Directory of Open Access Journals (Sweden)

    Sreedevi

    2008-01-01

    Full Text Available Background and Objectives: The importance of saliva for oral health is well known. Diabetes mellitus affects the salivary gland functioning and thus alters the salivary constituents. For many years the question of the presence of glucose in saliva has been a subject of debate and only few people found correlation between serum glucose and salivary glucose in diabetics. Hence, the purpose of this study was to estimate and correlate salivary glucose concentration and serum glucose concentration in diabetics and healthy controls. Materials and Methods: 60 newly diagnosed diabetic patients and 60 age and sex matched control subjects were included in the study. Blood and saliva samples from both the groups were collected at least two hours after the breakfast. The samples were centrifuged and subjected to glucose analysis using Semiautoanalyzer (BioSystems BTS-310 Photometer. For experimental group, the samples were collected again after the control of diabetes mellitus. The statistical comparisons were performed using paired and unpaired t -test. Results: A highly significant correlation was found between salivary glucose and serum glucose before the treatment and also after the control of diabetes. The correlation between salivary glucose and serum glucose was also highly significant in controls. The levels of salivary glucose did not vary with age and sex. Conclusion and Interpretation: As there was significant correlation between salivary glucose and serum glucose, salivary glucose holds the potential of being a marker in diabetes. Further, it has an added advantage of being non-invasive procedure with no need of special equipments and with fewer compliance problems as compared with collection of blood.

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

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  15. Effect of interleukin-1 and tumor necrosis factor/cachectin on glucose turnover in the rat

    International Nuclear Information System (INIS)

    Flores, E.A.; Istfan, N.; Pomposelli, J.J.; Blackburn, G.L.; Bistrian, B.R.

    1990-01-01

    We studied the effect of recombinant human interleukin-1 beta (IL-1) and recombinant human tumor necrosis factor alpha/cachectin (TNF) on glucose kinetics in healthy rats by means of a primed constant infusion of D-(6-3H)glucose and D-[U- 14 C]glucose. During the isotope (6-hour) and monokine (4-hour) infusion, plasma levels of glucagon and insulin were determined and correlated with changes in glucose metabolism. The rates of glucose appearance (Ra) and disappearance (Rd) were elevated only with IL-1 and were associated with an increase in glucagon and a concomitant decrease in the ratio of insulin to glucagon. Plasma glucose concentration was increased early after IL-1 administration and coincided with the peak in the Ra. The augmentation of the metabolic clearance rate (MCR) and percent of flux oxidized by IL-1 suggest that this monokine induces the utilization of glucose as a substrate. TNF administration failed to modify the Ra or Rd, percent of flux oxidized, or MCR. TNF-treated rats increased the percent of glucose recycling, but not the total rate of glucose production. The results of this experiment suggest that endogenous macrophage products participate in the diverse alterations of carbohydrate metabolism seen during injury and/or infection

  16. Glucose allostasis

    DEFF Research Database (Denmark)

    Stumvoll, Michael; Tataranni, P Antonio; Stefan, Norbert

    2003-01-01

    In many organisms, normoglycemia is achieved by a tight coupling of nutrient-stimulated insulin secretion in the pancreatic beta-cell (acute insulin response [AIR]) and the metabolic action of insulin to stimulate glucose disposal (insulin action [M]). It is widely accepted that in healthy...... individuals with normal glucose tolerance, normoglycemia can always be maintained by compensatorily increasing AIR in response to decreasing M (and vice versa). This has been mathematically described by the hyperbolic relationship between AIR and M and referred to as glucose homeostasis, with glucose...... concentration assumed to remain constant along the hyperbola. Conceivably, glucose is one of the signals stimulating AIR in response to decreasing M. Hypothetically, as with any normally functioning feed-forward system, AIR should not fully compensate for worsening M, since this would remove the stimulus...

  17. Glucose repression in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Kayikci, Omur; Nielsen, Jens

    2015-01-01

    Glucose is the primary source of energy for the budding yeast Saccharomyces cerevisiae. Although yeast cells can utilize a wide range of carbon sources, presence of glucose suppresses molecular activities involved in the use of alternate carbon sources as well as it represses respiration...... and gluconeogenesis. This dominant effect of glucose on yeast carbon metabolism is coordinated by several signaling and metabolic interactions that mainly regulate transcriptional activity but are also effective at post-transcriptional and post-translational levels. This review describes effects of glucose repression...... on yeast carbon metabolism with a focus on roles of the Snf3/Rgt2 glucose-sensing pathway and Snf1 signal transduction in establishment and relief of glucose repression....

  18. PPARδ activation in human myotubes increases mitochondrial fatty acid oxidative capacity and reduces glucose utilization by a switch in substrate preference.

    NARCIS (Netherlands)

    Feng, Yan; Nikolic, Natasa; Bakke, Siril S.; Boekschoten, Mark; Kersten, Sander; Kase, Eili T.; Rustan, Arild C.; Thoresen, G.H.

    2014-01-01

    The role of peroxisome proliferator-activated receptor δ (PPARδ) activation on global gene expression and mitochondrial fuel utilization were investigated in human myotubes. Only 21 genes were up-regulated and 3 genes were down-regulated after activation by the PPARδ agonist GW501516. Pathway

  19. PPARδ activation in human myotubes increases mitochondrial fatty acid oxidative capacity and reduces glucose utilization by a switch in substrate preference

    NARCIS (Netherlands)

    Feng, Y.; Nikolic, N.; Bakke, S.S.; Kersten, A.H.; Boekschoten, M.V.

    2014-01-01

    The role of peroxisome proliferator-activated receptor d (PPARd) activation on global gene expression and mitochondrial fuel utilization were investigated in human myotubes. Only 21 genes were up-regulated and 3 genes were down-regulated after activation by the PPARd agonist GW501516. Pathway

  20. Effect of somatostatin on glucose homeostasis in conscious long-fasted dogs

    Energy Technology Data Exchange (ETDEWEB)

    Stevenson, R.W.; Steiner, K.E.; Hendrick, G.K.; Cherrington, A.D. (Vanderbilt Univ. School of Medicine, Nashville, TN (USA))

    1987-10-01

    The effects of somatostatin plus intraportal insulin and glucagon replacement (pancreatic clamp) on carbohydrate metabolism were studied in conscious dogs fasted for 7 days so that gluconeogenesis was a major contributor to total glucose production. By use of (3-{sup 3}H)glucose, glucose production (R{sub a}) and utilization (R{sub d}) and glucose clearance were assessed before and after implementation of the pancreatic clamp. After an initial control period, somatostatin (0.8 {mu}g{center dot}kg{sup {minus}1}{center dot}min{sup {minus}1}) was infused with intraportal replacement amounts of glucagon and insulin. The insulin infusion rate was varied to maintain euglycemia and then kept constant for 250 min. Plasma glucagon was similar before and during somatostatin infusion, while plasma insulin was lower. Plasma glucose levels remained similar while R{sub a} and R{sub d} and the ratio of glucose clearance to plasma insulin were significantly increased. Net hepatic lactate uptake and ({sup 14}C)alanine plus ({sup 14}C)lactate conversion to ({sup 14}C)glucose increased. In conclusion, somatostatin alters glucose clearance in 7-day fasted dogs, resulting in changes in several indices of carbohydrate metabolism.

  1. Deletion of apoptosis signal-regulating kinase 1 (ASK1 protects pancreatic beta-cells from stress-induced death but not from glucose homeostasis alterations under pro-inflammatory conditions.

    Directory of Open Access Journals (Sweden)

    Emilie Pepin

    Full Text Available Type 2 diabetes is characterized by pancreatic beta-cell dysfunction and is associated with low-grade inflammation. Recent observations suggest that apoptosis signal-regulating kinase 1 (ASK1 is involved in beta-cell death in response to different stressors. In this study, we tested whether ASK1 deficiency protects beta-cells from glucolipotoxic conditions and cytokines treatment or from glucose homeostasis alteration induced by endotoxemia.Insulin secretion was neither affected upon shRNA-mediated downregulation of ASK1 in MIN6 cells nor in islets from ASK1-deficient mice. ASK1 silencing in MIN6 cells and deletion in islets did not prevent the deleterious effect of glucolipotoxic conditions or cytokines on insulin secretion. However, it protected MIN6 cells from death induced by ER stress or palmitate and islets from short term caspase activation in response to cytokines. Moreover, endotoxemia induced by LPS infusion increased insulin secretion during hyperglycemic clamps but the response was similar in wild-type and ASK1-deficient mice. Finally, insulin sensitivity in the presence of LPS was not affected by ASK1-deficiency.Our study demonstrates that ASK1 is not involved in beta-cell function and dysfunction but controls stress-induced beta-cell death.

  2. Alterations in grooming activity and syntax in heterozygous SERT and BDNF knockout mice: the utility of behavior-recognition tools to characterize mutant mouse phenotypes.

    Science.gov (United States)

    Kyzar, Evan J; Pham, Mimi; Roth, Andrew; Cachat, Jonathan; Green, Jeremy; Gaikwad, Siddharth; Kalueff, Allan V

    2012-12-01

    Serotonin transporter (SERT) and brain-derived neurotrophic factor (BDNF) are key modulators of molecular signaling, cognition and behavior. Although SERT and BDNF mutant mouse phenotypes have been extensively characterized, little is known about their self-grooming behavior. Grooming represents an important behavioral domain sensitive to environmental stimuli and is increasingly used as a model for repetitive behavioral syndromes, such as autism and attention deficit/hyperactivity disorder. The present study used heterozygous ((+/-)) SERT and BDNF male mutant mice on a C57BL/6J background and assessed their spontaneous self-grooming behavior applying both manual and automated techniques. Overall, SERT(+/-) mice displayed a general increase in grooming behavior, as indicated by more grooming bouts and more transitions between specific grooming stages. SERT(+/-) mice also aborted more grooming bouts, but showed generally unaltered activity levels in the observation chamber. In contrast, BDNF(+/-) mice displayed a global reduction in grooming activity, with fewer bouts and transitions between specific grooming stages, altered grooming syntax, as well as hypolocomotion and increased turning behavior. Finally, grooming data collected by manual and automated methods (HomeCageScan) significantly correlated in our experiments, confirming the utility of automated high-throughput quantification of grooming behaviors in various genetic mouse models with increased or decreased grooming phenotypes. Taken together, these findings indicate that mouse self-grooming behavior is a reliable behavioral biomarker of genetic deficits in SERT and BDNF pathways, and can be reliably measured using automated behavior-recognition technology. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Oral glucose-stimulated growth hormone (GH) test in adult GH deficiency patients and controls: Potential utility of a novel test.

    Science.gov (United States)

    Pena-Bello, Lara; Seoane-Pillado, Teresa; Sangiao-Alvarellos, Susana; Outeiriño-Blanco, Elena; Varela-Rodriguez, Barbara; Juiz-Valiña, Paula; Cordido, María; Cordido, Fernando

    2017-10-01

    The diagnosis of adult GH deficiency requires confirmation with a GH stimulation test. Oral glucose (OG) administration affects GH secretion, initially decreasing and subsequently stimulating GH secretion. The aim of this study was to investigate the diagnostic efficacy and safety of a long OG test (LOGT) as a stimulus of GH secretion for the diagnosis of adult GH deficiency (AGHD). Prospective experimental cross-sectional study. The study was conducted at the Endocrinology department of the University Hospital of a Coruña, Spain. We included 60 (40 women) AGHD patients (15) and controls (45) paired 1:3, of similar age, sex and BMI. The area under the curve (AUC) and peak were calculated for GH. The Mann-Whitney test was used to compare the different groups. ROC curve analyses were used. p-ValuesGH was obtained every 30min for a total of 300min. Peak GH area under receiver operating characteristic curve (ROC-AUC) following LOGT. Peak GH (μg/L) levels were lower in the AGHD patients (0.26±0.09) than in the controls (4.00±0.45), pGH cut-point was 1.0μg/L, with 100% sensitivity, 78% specificity, ROC-AUC of 0.9089 and 81.82% accuracy. There were no relevant adverse events during any of the LOGT. The LOGT could be a cheap, safe, convenient and effective test for the diagnosis of AGHD. Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  4. Development and use of a new perfusion technique to study glucose metabolism of the aortic wall in normal and alloxan-diabetic rabbits

    International Nuclear Information System (INIS)

    Brown, B.J.M.

    1985-01-01

    This study investigated (1) possible alterations in glucose uptake and utilization in the perfused, normal, and diabetic vascular wall of rabbits and (2) the effects thereon of insulin and exogenous glucose concentration. Part I involved development and characterization of an in vitro perfusion technique that closely reproduced predetermined in vivo conditions of aortic blood flow, arterial blood pressure, heart rate and pulse pressure. The responsiveness of the preparation to vasoactive agents was assessed with concentrations of norepinephrine (NE) from 10 -9 to 10 -4 M. In Part II, the effects of NE-induced tension development on glucose metabolism were determined by perfusion with oxygenated physiological salt solution (PSS) containing 7 mM glucose and tracer amounts of uniformly labeled 14 C-glucose. Aortas from 8 week-diabetic rabbits were perfused under similar conditions employing a NE infusion in the presence or absence of insulin (150 uU/ml) and variable levels of glucose. Effects of NE-induced tension development include an apparent increase (39%) in glucose uptake and a twofold increase in 14 CO 2 and lactate production. Aortas from diabetic rabbits perfused with PSS containing 7 mM glucose demonstrated marked decreases in glucose uptake (74%), 14 CO 2 (68%), lactate (30%), total tissue glycogen (75%) and labeled tissue phospholipids (70%). Insulin or elevation of exogenous glucose to 25 mM (diabetic levels) normalized glucose uptake, but had differential effects on the pattern of substrate utilization. The marked alterations of glucose metabolism in the diabetic state may contribute to the functional changes observed in diabetic blood vessels

  5. Glucose Binding Protein as a Novel Optical Glucose Nanobiosensor

    Directory of Open Access Journals (Sweden)

    Majed DWEIK

    2009-11-01

    Full Text Available Development of an in vivo optical sensor requires the utilization of Near Infra Red (NIR fluorophores due to their ability to operate within the biological tissue window. Alexa Fluor 750 (AF750 and Alexa Fluor 680 (AF680 were examined as potential NIR fluorophores for an in vivo fluorescence resonance energy transfer (FRET glucose biosensor. AF680 and AF750 found to be a FRET pair and percent energy transfer was calculated. Next, the tested dye pair was utilized in a competitive binding assay in order to detect glucose. Concanavalin A (Con A and dextran have binding affinity, but in the presence of glucose, glucose displaces dextran due to its higher affinity to Con A than dextran. Finally, the percent signal transfer through porcine skin was examined. The results showed with approximately 4.0 mm porcine skin thickness, 1.98 % of the fluorescence was transmitted and captured by the detector.

  6. Glucose allostasis

    DEFF Research Database (Denmark)

    Stumvoll, Michael; Tataranni, P Antonio; Stefan, Norbert

    2003-01-01

    (insulin resistance), we propose to use the term "glucose allostasis." Allostasis (stability through change) ensures the continued homeostatic response (stability through staying the same) to acute stress at some cumulative costs to the system. With increasing severity and over time, the allostatic load......In many organisms, normoglycemia is achieved by a tight coupling of nutrient-stimulated insulin secretion in the pancreatic beta-cell (acute insulin response [AIR]) and the metabolic action of insulin to stimulate glucose disposal (insulin action [M]). It is widely accepted that in healthy...

  7. 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.

  8. Altering the coenzyme preference of xylose reductase to favor utilization of NADH enhances ethanol yield from xylose in a metabolically engineered strain of Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Nidetzky Bernd

    2008-03-01

    Full Text Available Abstract Background Metabolic engineering of Saccharomyces cerevisiae for xylose fermentation into fuel ethanol has oftentimes relied on insertion of a heterologous pathway that consists of xylose reductase (XR and xylitol dehydrogenase (XDH and brings about isomerization of xylose into xylulose via xylitol. Incomplete recycling of redox cosubstrates in the catalytic steps of the NADPH-preferring XR and the NAD+-dependent XDH results in formation of xylitol by-product and hence in lowering of the overall yield of ethanol on xylose. Structure-guided site-directed mutagenesis was previously employed to change the coenzyme preference of Candida tenuis XR about 170-fold from NADPH in the wild-type to NADH in a Lys274→Arg Asn276→Asp double mutant which in spite of the structural modifications introduced had retained the original catalytic efficiency for reduction of xylose by NADH. This work was carried out to assess physiological consequences in xylose-fermenting S. cerevisiae resulting from a well defined alteration of XR cosubstrate specificity. Results An isogenic pair of yeast strains was derived from S. cerevisiae Cen.PK 113-7D through chromosomal integration of a three-gene cassette that carried a single copy for C. tenuis XR in wild-type or double mutant form, XDH from Galactocandida mastotermitis, and the endogenous xylulose kinase (XK. Overexpression of each gene was under control of the constitutive TDH3 promoter. Measurement of intracellular levels of XR, XDH, and XK activities confirmed the expected phenotypes. The strain harboring the XR double mutant showed 42% enhanced ethanol yield (0.34 g/g compared to the reference strain harboring wild-type XR during anaerobic bioreactor conversions of xylose (20 g/L. Likewise, the yields of xylitol (0.19 g/g and glycerol (0.02 g/g were decreased 52% and 57% respectively in the XR mutant strain. The xylose uptake rate per gram of cell dry weight was identical (0.07 ± 0.02 h-1 in both strains

  9. Noninvasive measurement of regional myocardial glucose metabolism by positron emission computed tomography. [Dogs

    Energy Technology Data Exchange (ETDEWEB)

    Schelbert, H.R.; Phelps, M.E.

    1980-06-01

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

  10. Injury timing alters metabolic, inflammatory and functional outcomes following repeated mild traumatic brain injury.

    Science.gov (United States)

    Weil, Zachary M; Gaier, Kristopher R; Karelina, Kate

    2014-10-01

    Repeated head injuries are a major public health concern both for athletes, and members of the police and armed forces. There is ample experimental and clinical evidence that there is a period of enhanced vulnerability to subsequent injury following head trauma. Injuries that occur close together in time produce greater cognitive, histological, and behavioral impairments than do injuries separated by a longer period. Traumatic brain injuries alter cerebral glucose metabolism and the resolution of altered glucose metabolism may signal the end of the period of greater vulnerability. Here, we injured mice either once or twice separated by three or 20days. Repeated injuries that were separated by three days were associated with greater axonal degeneration, enhanced inflammatory responses, and poorer performance in a spatial learning and memory task. A single injury induced a transient but marked increase in local cerebral glucose utilization in the injured hippocampus and sensorimotor cortex, whereas a second injury, three days after the first, failed to induce an increase in glucose utilization at the same time point. In contrast, when the second injury occurred substantially later (20days after the first injury), an increase in glucose utilization occurred that paralleled the increase observed following a single injury. The increased glucose utilization observed after a single injury appears to be an adaptive component of recovery, while mice with 2 injuries separated by three days were not able to mount this response, thus this second injury may have produced a significant energetic crisis such that energetic demands outstripped the ability of the damaged cells to utilize energy. These data strongly reinforce the idea that too rapid return to activity after a traumatic brain injury can induce permanent damage and disability, and that monitoring cerebral energy utilization may be a tool to determine when it is safe to return to the activity that caused the initial

  11. High Body Adiposity Drives Glucose Intolerance and Increases Cardiovascular Risk in Normoglycemic Subjects.

    Science.gov (United States)

    Pérez-Pevida, Belén; Díaz-Gutiérrez, Jesús; Miras, Alexander Dimitri; Silva, Camilo; Romero, Sonia; Salvador, Javier; Escalada, Javier; Frühbeck, Gema

    2018-03-09

    The objective of this study was to assess the utility of the 2-hour oral glucose tolerance test (OGTT) value to discriminate between different cardiometabolic profiles and examine the role of body composition in predicting the associated increased risk for glucose impairment, beta-cell dysfunction, and cardiovascular disease (CVD). Subjects with normal fasting glucose completed a 2-hour OGTT and were categorized to the carbohydrate metabolism alterations (CMAs) or the control group based on a 2-hour glucose threshold of 7.8 mmol/L. Body composition, visceral adipose tissue, OGTT-based parameters, and cardiovascular risk factors (CVRFs) such as hypertension, dyslipidemia, obstructive sleep apnea, nonalcoholic fatty liver disease, and smoking status were measured. Subjects with CMAs exhibited a significantly higher 1-hour postload glucose level and a greater decline in beta-cell function and CVRF profiles. After multivariate adjustment, an excess of total body and visceral fat was associated with an increased risk of CMAs, beta-cell dysfunction, CVRFs, and lower whole-body insulin sensitivity. These data support the etiopathogenic role of body and visceral fat in the development of glucose derangements and CVRFs early on in the metabolic dysregulation process. Thus, body composition analysis and OGTT assessment performed in individuals with normal fasting glucose enable a better identification of patients at risk of developing type 2 diabetes and CVD. © 2018 The Authors. Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS).

  12. Quantitative assessment of brain glucose metabolic rates using in vivo deuterium magnetic resonance spectroscopy.

    Science.gov (United States)

    Lu, Ming; Zhu, Xiao-Hong; Zhang, Yi; Mateescu, Gheorghe; Chen, Wei

    2017-11-01

    Quantitative assessment of cerebral glucose consumption rate (CMR glc ) and tricarboxylic acid cycle flux (V TCA ) is crucial for understanding neuroenergetics under physiopathological conditions. In this study, we report a novel in vivo Deuterium ( 2 H) MRS (DMRS) approach for simultaneously measuring and quantifying CMR glc and V TCA in rat brains at 16.4 Tesla. Following a brief infusion of deuterated glucose, dynamic changes of isotope-labeled glucose, glutamate/glutamine (Glx) and water contents in the brain can be robustly monitored from their well-resolved 2 H resonances. Dynamic DMRS glucose and Glx data were employed to determine CMR glc and V TCA concurrently. To test the sensitivity of this method in response to altered glucose metabolism, two brain conditions with different anesthetics were investigated. Increased CMR glc (0.46 vs. 0.28 µmol/g/min) and V TCA (0.96 vs. 0.6 µmol/g/min) were found in rats under morphine as compared to deeper anesthesia using 2% isoflurane. This study demonstrates the feasibility and new utility of the in vivo DMRS approach to assess cerebral glucose metabolic rates at high/ultrahigh field. It provides an alternative MRS tool for in vivo study of metabolic coupling relationship between aerobic and anaerobic glucose metabolisms in brain under physiopathological states.

  13. Glucose-Sensing in the Reward System

    NARCIS (Netherlands)

    Koekkoek, Laura L.; Mul, Joram D.; la Fleur, Susanne E.

    2017-01-01

    Glucose-sensing neurons are neurons that alter their activity in response to changes in extracellular glucose. These neurons, which are an important mechanism the brain uses to monitor changes in glycaemia, are present in the hypothalamus, where they have been thoroughly investigated. Recently,

  14. Regulation and control of glucose overutilization in erythrocytes by vanadate.

    Science.gov (United States)

    Baquer, N Z; Saxena, A K; Srivastava, P

    The insulin mimetic effect of vanadate in in vitro incubation of erythrocytes with high glucose concentrations showed an increase in sorbitol accumulation and glucose utilization using U-14C-glucose. Aldose reductase inhibitors and vanadate addition reversed the sorbitol accumulation, whereas insulin could not reverse it. Increased glucose utilization was also normalized with vanadium compounds. Increased activity of aldose reductase and sorbitol levels in diabetic animals were also normalized with vanadate treatment.

  15. A mutation in the COX5 gene of the yeast Scheffersomyces stipitis alters utilization of amino acids as carbon source, ethanol formation and activity of cyanide insensitive respiration.

    Science.gov (United States)

    Freese, Stefan; Passoth, Volkmar; Klinner, Ulrich

    2011-04-01

    Scheffersomyces stipitis PJH was mutagenized by random integrative mutagenesis and the integrants were screened for lacking the ability to grow with glutamate as sole carbon source. One of the two isolated mutants was damaged in the COX5 gene, which encodes a subunit of the cytochrome c oxidase. BLAST searches in the genome of Sc. stipitis revealed that only one singular COX5 gene exists in Sc. stipitis, in contrast to Saccharomyces cerevisiae, where two homologous genes are present. Mutant cells had lost the ability to grow with the amino acids glutamate, proline or aspartate and other non-fermentable carbon sources, such as acetic acid and ethanol, as sole carbon sources. Biomass formation of the mutant cells in medium containing glucose or xylose as carbon source was lower compared with the wild-type cells. However, yields and specific ethanol formation of the mutant were much higher, especially under conditions of higher aeration. The mutant cells lacked both cytochrome c oxidase activity and cyanide-sensitive respiration, whereas ADH and PDC activities were distinctly enhanced. SHAM-sensitive respiration was obviously essential for the fermentative metabolism, because SHAM completely abolished growth of the mutant cells with both glucose or xylose as carbon source. Copyright © 2011 John Wiley & Sons, Ltd.

  16. Short communication: amino acid supplementation and stage of lactation alter apparent utilization of nutrients by blood neutrophils from lactating dairy cows in vitro

    Science.gov (United States)

    Glutamine is the preferred AA used by polymorphonuclear leukocytes (PMN) during the inflammatory response. However, the effect of other AA on bovine PMN response during inflammation and how this is altered by stage of lactation has not been fully elucidated. The objective of this study was to dete...

  17. Glucose prediction by analysis of exhaled metabolites - a systematic review

    NARCIS (Netherlands)

    Leopold, Jan Hendrik; van Hooijdonk, Roosmarijn T. M.; Sterk, Peter J.; Abu-Hanna, Ameen; Schultz, Marcus J.; Bos, Lieuwe D. J.

    2014-01-01

    Background: In critically ill patients, glucose control with insulin mandates time-and blood-consuming glucose monitoring. Blood glucose level fluctuations are accompanied by metabolomic changes that alter the composition of volatile organic compounds (VOC), which are detectable in exhaled breath.

  18. Deficient Rab11 activity underlies glucose hypometabolism in primary neurons of Huntington's disease mice

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xueyi, E-mail: xli12@partners.org [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States); Valencia, Antonio; McClory, Hollis; Sapp, Ellen; Kegel, Kimberly B. [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States); DiFiglia, Marian, E-mail: difiglia@helix.mgh.harvard.edu [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer Primary Huntington's disease neurons are impaired in taking up glucose. Black-Right-Pointing-Pointer Rab11 modulates glucose uptake in neurons. Black-Right-Pointing-Pointer Increasing Rab11 activity attenuates the glucose uptake defect in disease neurons. Black-Right-Pointing-Pointer We provide a novel mechanism for glucose hypometabolism in Huntington's disease. -- Abstract: Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Positron emission tomography studies have revealed a decline in glucose metabolism in the brain of patients with HD by a mechanism that has not been established. We examined glucose utilization in embryonic primary cortical neurons of wild-type (WT) and HD knock-in mice, which have 140 CAG repeats inserted in the endogenous mouse huntingtin gene (HD{sup 140Q/140Q}). Primary HD{sup 140Q/140Q} cortical neurons took up significantly less glucose than did WT neurons. Expression of permanently inactive and permanently active forms of Rab11 correspondingly altered glucose uptake in WT neurons, suggesting that normal activity of Rab11 is needed for neuronal uptake of glucose. It is known that Rab11 activity is diminished in HD{sup 140Q/140Q} neurons. Expression of dominant active Rab11 to enhance the activity of Rab11 normalized glucose uptake in HD{sup 140Q/140Q} neurons. These results suggest that deficient activity of Rab11 is a novel mechanism for glucose hypometabolism in HD.

  19. Acurácia, utilidade e complicações da monitorização subcutânea contínua da glicose (CGMS em pacientes pediátricos com diabetes tipo 1 Accuracy, utility and complications of continuous glucose monitoring system (CGMS in pediatric patients with type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Frederico F. R. Maia

    2005-08-01

    Full Text Available OBJETIVO: Avaliar a acurácia, utilidade e complicações da monitorização subcutânea contínua da glicemia em crianças e adolescentes com diabetes melito tipo 1 (DM1. MÉTODOS: Foram estudados retrospectivamente 16 pacientes (16,12±4,41 anos, submetidos à monitorização subcutânea contínua da glicemia (Medtronic; Northridge, CA, EUA por 72 horas. Foram analisados os valores de glicemia capilar média e pelo sensor monitorização subcutânea contínua da glicemia; excursões glicêmicas (monitorização subcutânea contínua da glicemia versus. glicemia capilar; hiperglicemia pós-prandial (OBJECTIVE: To evaluate the accuracy, utility and complications of continuous glucose monitoring system in children and adolescents with type 1 diabetes. METHODS: This retrospective study assessed 16 type 1 diabetic patients (16.12±4.41 years submitted to continuous glucose monitoring system (Medtronic; Northridge, CA for 72 hours. The following parameters were analyzed: mean capillary glucose level and mean glucose value measured by the continuous glucose monitoring system; glucose excursions (continuous glucose monitoring system vs. capillary glucose measurement, postprandial hyperglycemia (NR < 140 mg/dl, nocturnal hypoglycemia, complications (trauma, local infection, disconnection and therapeutic management after continuous glucose monitoring. A1c levels were measured at the beginning and after 3 months of the study. RESULTS: The mean capillary glucose values were 214.3±66.5 mg/dl vs. 207.6±54.6 mg/dl by continuous glucose monitoring system, with a significant correlation (p = 0.001. The correlation coefficient and mean absolute error were 0.86±0.21 and 12.6% of the median, respectively. The continuous glucose monitoring system was significantly more efficient in detecting glucose excursion than fingerstick capillary blood sampling (p = 0.04; W = 74, and postprandial hyperglycemia was identified in 60% of type 1 diabetic patients with a

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

    Science.gov (United States)

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

    2011-01-01

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

  1. Glucose and cardiovascular risk

    NARCIS (Netherlands)

    Fuchs, M.; Hoekstra, J. B. L.; Mudde, A. H.

    2002-01-01

    The American Diabetes Association and the World Health Organisation have recently redefined the spectrum of abnormal glucose tolerance. The criteria for diabetes mellitus were sharpened and impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were classified as intermediate stages

  2. Altered Immune Response of the Rice Frog Fejervarya limnocharis Living in Agricultural Area with Intensive Herbicide Utilization at Nan Province, Thailand

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    Khattapan Jantawongsri

    2015-01-01

    Full Text Available Herbicides (atrazine, glyphosate and paraquat have been intensively used in Nan Province for a long time. Prior observations indicated that herbicide contamination and adverse health effects were found on the rice frog Fejervarya limnocharis living in paddy fields at Nan Province. Contamination of herbicides may influence disease emergence by acting directly or indirectly upon the immune system of amphibian or by causing disruptions in homeostasis, it is thus interesting to investigate potential effects of herbicide contamination in Nan Province on immune responses of the rice frog living in agricultural areas. Frogs were caught from a paddy field with no history of herbicide utilization (reference site and a paddy field with intensive herbicide utilization (contaminated site during 2010-2011. After dissection, frog livers were fixed in 10% neutral buffer formalin, processed by paraffin method and stained with hematoxylin and eosin. Number of melanomacrophage and melanomacrophage center (MMC were counted under a light microscope and used as markers of non-specific immune response. It was found that there was no significant sex-related difference in these numbers. However, there were significant seasonal differences in these numbers in both reference and contaminated site frogs, suggesting that seasonal difference in herbicide usage tend to affect frog's immune system in agricultural areas. Furthermore, numbers of melanomacrophage and MMC in early wet, late wet and early dry periods were markedly higher in the contaminated site frogs compared to those of the reference site frogs. The observation on amphibian's immune response to environmental contaminants could indicate the impacts of herbicide utilization on other vertebrates, as well as its role in amphibian declines.

  3. Expression and Regulation of Facilitative Glucose Transporters in Equine Insulin-Sensitive Tissue: From Physiology to Pathology

    Science.gov (United States)

    Lacombe, Véronique A.

    2014-01-01

    Glucose uptake is the rate-limiting step in glucose utilization in mammalians and is tightly regulated by a family of specialized proteins, called the facilitated glucose transporters (GLUTs/SLC2). GLUT4, the major isoform in insulin-responsive tissue, translocates from an intracellular pool to the cell surface and as such determines insulin-stimulated glucose uptake. However, despite intensive research over 50 years, the insulin-dependent and -independent pathways that mediate GLUT4 translocation are not fully elucidated in any species. Insulin resistance (IR) is one of the hallmarks of equine metabolic syndrome and is the most common metabolic predisposition for laminitis in horses. IR is characterized by the impaired ability of insulin to stimulate glucose disposal into insulin-sensitive tissues. Similar to other species, the functional capability of the insulin-responsive GLUTs is impaired in muscle and adipose tissue during IR in horses. However, the molecular mechanisms of altered glucose transport remain elusive in all species, and there is still much to learn about the physiological and pathophysiological functions of the GLUT family members, especially in regard to class III. Since GLUTs are key regulators of whole-body glucose homeostasis, they have received considerable attention as potential therapeutic targets to treat metabolic disorders in human and equine patients. PMID:24977043

  4. Glucose metabolism in pregnant sheep when placental growth is restricted

    International Nuclear Information System (INIS)

    Owens, J.A.; Falconer, J.; Robinson, J.S.

    1989-01-01

    The effect of restricting placental growth on glucose metabolism in pregnant sheep in late gestation was determined by primed constant infusions of D-[U- 14 C]- and D-[2- 3 H]glucose and antipyrine into fetuses of six control sheep and six sheep from which endometrial caruncles had been removed before pregnancy (caruncle sheep). In the latter, placental and fetal weights were reduced, as was the concentration of glucose in fetal arterial blood. Fetal glucose turnover in caruncle sheep was only 52-59% of that in controls, largely because of lower umbilical loss of glucose back to the placenta (38-39% of control) and lower fetal glucose utilization (61-74% of control). However, fetal glucose utilization on a weight-specific basis was similar in control and caruncle sheep. Significant endogenous glucose production occurred in control and caruncle fetal sheep. Maternal glucose production and partition of glucose between the gravid uterus and other maternal tissues were similar in control and caruncle sheep. In conclusion, when placental and fetal growth are restricted, fetal glucose utilization is maintained by reduced loss of glucose back to the placenta and mother and by maintaining endogenous glucose production

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

    Science.gov (United States)

    Alsahli, Mazen; Gerich, John E

    2017-11-01

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

  6. Underestimation of hepatic glucose production by radioactive and stable tracers

    International Nuclear Information System (INIS)

    Argoud, G.M.; Schade, D.S.; Eaton, R.P.

    1987-01-01

    Although negative hepatic glucose production rates are physiologically impossible, they have been observed when hepatic glucose production is measured with the tracer-dilution technique during the hyperinsulinemic, euglycemic glucose clamp. Because hepatic glucose production is determined from the difference between tracer-derived glucose disposal and the known exogenous glucose infusion rate, the negative values for hepatic glucose production must result from an underestimation of glucose disposal by the tracer technique. In the current investigation, tracer-derived glucose disposal was measured in 25 subjects undergoing hyperinsulinemic, euglycemic clamps. Glucose disposal was measured with both radioactive and stable isotopes that utilize different methodologies, to determine whether discriminant metabolism of the isotopes versus methodological error leads to underestimation of tracer-derived glucose disposal. Both the radioactive and stable methodologies underestimated the exogenous glucose infusion rate during the hyperinsulinemic euglycemic clamp by 27 and 17%, respectively. Mean hepatic glucose production was -2.1 +/- 0.2 and -1.3 +/- 0.2 mg X kg-1 X min-1 as determined by the radioactive and stable isotope methodologies, respectively. Methodological error was an unlikely cause of this underestimation because it occurred with two different methodologies. The most likely explanation for underestimated rates of glucose disposal determined by the two types of isotope methodologies is discrepant metabolism of glucose tracers in comparison with unlabeled glucose

  7. Defining the effect and mediators of two knowledge translation strategies designed to alter knowledge, intent and clinical utilization of rehabilitation outcome measures: a study protocol [NCT00298727

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    Law Mary

    2006-07-01

    Full Text Available Abstract Background A substantial number of valid outcome measures have been developed to measure health in adult musculoskeletal and childhood disability. Regrettably, national initiatives have merely resulted in changes in attitude, while utilization remains unacceptably low. This study will compare the effectiveness and mediators of two different knowledge transfer (KT interventions in terms of their impact on changing knowledge and behavior (utilization and clinical reasoning related to health outcome measures. Method/Design Physical and occupational therapists (n = 144 will be recruited in partnership with the national professional associations to evaluate two different KT interventions with the same curriculum: 1 Stakeholder-Hosted Interactive Problem-Based Seminar (SHIPS, and 2 Online Problem-Based course (e-PBL. SHIPS will consist of face-to-face problem-based learning (PBL for 2 1/2 days with outcome measure developers as facilitators, using six problems generated in consultation with participants. The e-PBL will consist of a 6-week web-based course with six generic problems developed by content experts. SHIPS will be conducted in three urban centers in Canada. Participants will be block-allocated by a minimization procedure to either of the two interventions to minimize any prognostic differences. Trained evaluators at each site will conduct chart audits and chart-stimulated recall. Trained interviewers will conduct semi-structured interviews focused on identifying critical elements in KT and implementing practice changes. Interviews will be transcribed verbatim. Baseline predictors including demographics, knowledge, attitudes/barriers regarding outcome measures, and Readiness to Change will be assessed by self-report. Immediately post-intervention and 6 months later, these will be re-administered. Primary qualitative and quantitative evaluations will be conducted 6-months post-intervention to assess the relative effectiveness of KT

  8. Alteration of 15N /14N and 13C /12C ratios of plant matter during the initial stages of diagenesis: Studies utilizing archaeological specimens from Peru

    Science.gov (United States)

    DeNiro, Michael J.; Hastorf, Christine A.

    1985-01-01

    The stable carbon and nitrogen isotope ratios of plants extracted from Peruvian archaeological sites, ranging in age from 400 to 4000 years B.P., have been measured. The δ13C and δ15N values of prehistoric plants that were carbonized prior to deposition are similar to those of modern plants which have the same carbon dioxide fixation or nitrogen assimilation mechanisms. In contrast, the δ15N values of prehistoric plants that were not carbonized are generally 10-20%. and as much as 35%. more positive than those of their modern counterparts. The δ13C and δ15N values of different parts of prehistoric uncarbonized plants differ by as much as 8%. and 21%. respectively, whereas the same parts of modern plants have δ13C or δ15N values that lie within 2%. of one another. SEM analysis etiminated the possibility that diagenetic alteration of the isotope ratios of the prehistoric uncarbonized plants was caused by the adsorption of particulate soil matter. Isotopic analysis of the organic residues that remained after the prehistoric uncarbonized plants were treated to remove fractions that might have been added in the depositional environment indicated that the alteration of the δ13C values resulted from the adsorption of humic and fulvic acids, whereas the diagenetic shifts of the nitrogen isotope ratios were not caused by adsorption of δ15N-enriched organic or inorganic forms of nitrogen from the soil. Our observations do not permit us to speculate on a mechanism that accounts for the δ13N-enrichment of the prehistoric uncarbonized plant remains, although the excellent state of preservation of these samples suggests that isotopic fractionation during microbial decomposition was not the cause. The observation that the isotope ratios of the prehistoric carbonized plants are similar to those of their modern counterparts indicates that it will be possible to separate carbonized plants residues into three groups—legumes, non-leguminous C 3 plants or C 4 and CAM

  9. Mechanisms by which low glucose enhances the cytotoxicity of metformin to cancer cells both in vitro and in vivo.

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    Yongxian Zhuang

    Full Text Available Different cancer cells exhibit altered sensitivity to metformin treatment. Recent studies suggest these findings may be due in part to the common cell culture practice of utilizing high glucose, and when glucose is lowered, metformin becomes increasingly cytotoxic to cancer cells. In low glucose conditions ranging from 0 to 5 mM, metformin was cytotoxic to breast cancer cell lines MCF7, MDAMB231 and SKBR3, and ovarian cancer cell lines OVCAR3, and PA-1. MDAMB231 and SKBR3 were previously shown to be resistant to metformin in normal high glucose medium. When glucose was increased to 10 mM or above, all of these cell lines become less responsive to metformin treatment. Metformin treatment significantly reduced ATP levels in cells incubated in media with low glucose (2.5 mM, high fructose (25 mM or galactose (25 mM. Reductions in ATP levels were not observed with high glucose (25 mM. This was compensated by enhanced glycolysis through activation of AMPK when oxidative phosphorylation was inhibited by metformin. However, enhanced glycolysis was either diminished or abolished by replacing 25 mM glucose with 2.5 mM glucose, 25 mM fructose or 25 mM galactose. These findings suggest that lowering glucose potentiates metformin induced cell death by reducing metformin stimulated glycolysis. Additionally, under low glucose conditions metformin significantly decreased phosphorylation of AKT and various targets of mTOR, while phospho-AMPK was not significantly altered. Thus inhibition of mTOR signaling appears to be independent of AMPK activation. Further in vivo studies using the 4T1 breast cancer mouse model confirmed that metformin inhibition of tumor growth was enhanced when serum glucose levels were reduced via low carbohydrate ketogenic diets. The data support a model in which metformin treatment of cancer cells in low glucose medium leads to cell death by decreasing ATP production and inhibition of survival signaling pathways. The enhanced

  10. Dietary Salba (Salvia hispanica L) seed rich in α-linolenic acid improves adipose tissue dysfunction and the altered skeletal muscle glucose and lipid metabolism in dyslipidemic insulin-resistant rats.

    Science.gov (United States)

    Oliva, M E; Ferreira, M R; Chicco, A; Lombardo, Y B

    2013-10-01

    This work reports the effect of dietary Salba (chia) seed rich in n-3 α-linolenic acid on the morphological and metabolic aspects involved in adipose tissue dysfunction and the mechanisms underlying the impaired glucose and lipid metabolism in the skeletal muscle of rats fed a sucrose-rich diet (SRD). Rats were fed a SRD for 3 months. Thereafter, half the rats continued with SRD while in the other half, corn oil (CO) was replaced by chia seed for 3 months (SRD+chia). In control group, corn starch replaced sucrose. The replacement of CO by chia seed in the SRD reduced adipocyte hypertrophy, cell volume and size distribution, improved lipogenic enzyme activities, lipolysis and the anti-lipolytic action of insulin. In the skeletal muscle lipid storage, glucose phosphorylation and oxidation were normalized. Chia seed reversed the impaired insulin stimulated glycogen synthase activity, glycogen, glucose-6-phosphate and GLUT-4 protein levels as well as insulin resistance and dyslipidemia. © 2013 Elsevier Ltd. All rights reserved.

  11. CSF glucose test

    Science.gov (United States)

    Glucose test - CSF; Cerebrospinal fluid glucose test ... The glucose level in the CSF should be 50 to 80 mg/100 mL (or greater than 2/3 ... Abnormal results include higher and lower glucose levels. Abnormal ... or fungus) Inflammation of the central nervous system Tumor

  12. Glucose turnover, gluconeogenesis from glycerol, and estimation of net glucose cycling in cancer patients

    International Nuclear Information System (INIS)

    Lundholm, K.; Edstroem, S.; Karlberg, I.; Ekman, L.; Schersten, T.

    1982-01-01

    A double isotope method was used in patients with progressive malignancy and in control patients to measure: glucose turnover, conversion rate of carbon skeleton of glycerol into glucose, and the interorgan cycling of glucose carbons (Cori-cycle plus alanine-glucose cycle). [U- 14 C]glycerol and [6- 3 H]glucose were given intravenously as a single dose injection. The time course of the specific radioactivities of [6- 3 H] and [U- 14 C]glucose was followed in blood. The pool size and the turnover rate of glucose were increased in the cancer group as compared with the control patients. The net recycling of glucose carbons was not increased in the cancer group, despite the increased turnover of glucose. The alterations in the metabolism of glucose did not correlate with the plasma levels of insulin or thyroid hormones (T4, T3, rT3) neither in the entire cancer group nor in those cancer patients who were repeatedly investigated at different intervals of time. The turnover rate of glucose in the cancer patients correlated inversely to their body weight index. The gluconeogenesis rate, given as the fractional conversion rate of the injected radioactive dose of [ 14 C]glycerol, or as mol glucose . kg body weight-1 . day-1, was increased in the cancer group, but still contributed only 3% of the glucose turnover rate in both cancer and control patients. We conclude that an increased gluconeogenesis from glycerol is not significant in terms of energy expenditure in patients with progressive malignancy, as has previously been concluded for the gluconeogenesis from alanine. It seems that increased turnover of glucose may contribute to inappropriately high energy expenditure in cancer patients

  13. Utility of 75-g oral glucose tolerance test results and hemoglobin a1c values for predicting the incidence of diabetes mellitus among middle-aged Japanese men -a large-scale retrospective cohort study performed at a single hospital.

    Science.gov (United States)

    Fujibayashi, Kazutoshi; Yokokawa, Hirohide; Gunji, Toshiaki; Sasabe, Noriko; Okumura, Mitsue; Iijima, Kimiko; Haniu, Tomomi; Hisaoka, Teruhiko; Fukuda, Hiroshi

    2015-01-01

    The aim of this study was to investigate the associations between the incidence of diabetes and the accumulation of markers of impaired glucose metabolism; i.e., pre-diabetes. This retrospective cohort study recruited 1,631 men without diabetes at baseline who attended more than two routine health check-ups at our institution between 2006 and 2012. The participants were divided into four groups based on the number of markers of impaired glucose metabolism exhibited at the initial examination. The following markers of impaired glucose metabolism were defined as risk factors for diabetes: a fasting plasma glucose level of ≥110 mg/dL, 2-hour plasma glucose level of ≥140 mg/dL and glycated hemoglobin (HbA1c) value of ≥6.0% (42 mmol/moL). The risk of developing diabetes was assessed using a multivariate analysis. The median examination interval was 1,092 days. The incidence of diabetes rose in association with the number of markers. The subjects with two markers displayed a multivariate-adjusted odds ratio (OR) for diabetes of 19.43 [95% confidence interval (CI): 9.70-38.97] and the subjects with three markers displayed an OR of 48.30 (95% CI: 20.39-115.85) compared with the subjects with one or no markers. The present results demonstrate the impact of accumulating markers of impaired glucose metabolism on the risk of developing diabetes. Anti-diabetes intervention strategies should aim to comprehensively assess an individual's risk of developing diabetes at the pre-diabetes stage.

  14. The complete control of glucose level utilizing the composition of ketogenic diet with the gluconeogenesis inhibitor, the anti-diabetic drug metformin, as a potential anti-cancer therapy.

    Science.gov (United States)

    Oleksyszyn, Józef

    2011-08-01

    In the animal models of glucose dependent cancer growth, the growth is decreased 15-30% through the use of low-carbohydrate, calorically restricted and/or ketogenic diet. The remaining growth depends on glucose formed by the liver-kidney gluconeogenesis as is the case in the cancer cachexia. It is hypothesized that a new treatment for cancer diseases should be explored which includes the ketogenic diet combined with the inhibition of gluconeogenesis by the anti-diabetic drug metformin. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. The acute effect of metformin on glucose production in the conscious dog is primarily attributable to inhibition of glycogenolysis.

    Science.gov (United States)

    Chu, C A; Wiernsperger, N; Muscato, N; Knauf, M; Neal, D W; Cherrington, A D

    2000-12-01

    Although metformin has been used worldwide to treat type 2 diabetes for several decades, its mechanism of action on glucose homeostasis remains controversial. To further assess the effect of metformin on glucose metabolism, 10 42-hour-fasted conscious dogs were studied in the absence ([Con] n = 5) and presence ([Met] n = 5) of a portal infusion of metformin (0.15 mg x kg(-1) x min(-1)) over 300 minutes. Hepatic glucose production was measured by both arteriovenous-difference and tracer methods. All dogs were maintained on a pancreatic clamp and in a euglycemic state to ensure that any changes in glucose metabolism would result directly from the effects of metformin. The arterial metformin level was 21 +/- 3 microg/mL during the test period. Net hepatic glucose output (NHGO) decreased in Met dogs from 1.9 +/- 0.2 to 0.7 +/- 0.1 mg x kg(-1) x min(-1) (P dogs (1.7 +/- 0.3 to 1.5 +/- 0.3 mg x kg(-1)min(-1)). Tracer-determined glucose production paralleled NHGO. The net hepatic glycogenolytic rate decreased from 1.0 +/- 0.2 to -0.3 +/- 0.2 mg x kg(-1) x min(-1) (P dogs, but remained unchanged in Con dogs (0.8 +/- 0.2 to 0.8 +/- 0.3 mg x kg(-1) x min(-1)). No significant change in gluconeogenic flux was found in eitherthe Metgroup (1.2 +/- 0.3 to 1.3 +/- 0.3 mg x kg(-1) x min(-1)) or the Con group (1.3 +/- 0.4 to 1.0 +/- 0.3 mg x kg(-1) x min(-1)). No significant changes were observed in glucose utilization or glucose clearance in either group. In conclusion, in the normal fasted dog, (1) the primary acute effect of metformin on glucose metabolism was an inhibition of hepatic glucose production and not a stimulation of glucose utilization; and (2) the inhibition of glucose production was attributable to a decrease in hepatic glycogenolysis and not to an alteration in gluconeogenic flux.

  16. Could post-weaning dietary chia seed mitigate the development of dyslipidemia, liver steatosis and altered glucose homeostasis in offspring exposed to a sucrose-rich diet from utero to adulthood?

    Science.gov (United States)

    Fortino, M A; Oliva, M E; Rodriguez, S; Lombardo, Y B; Chicco, A

    2017-01-01

    The present work analyzes the effects of dietary chia seeds during postnatal life in offspring exposed to a sucrose-rich diet (SRD) from utero to adulthood. At weaning, chia seed (rich in α-linolenic acid) replaced corn oil (rich in linoleic acid) in the SRD. At 150 days of offspring life, anthropometrical parameters, blood pressure, plasma metabolites, hepatic lipid metabolism and glucose homeostasis were analyzed. Results showed that chia was able to prevent the development of hypertension, liver steatosis, hypertriglyceridemia and hypercholesterolemia. Normal triacylglycerol secretion and triacylglycerol clearance were accompanied by an improvement of de novo hepatic lipogenic and carnitine-palmitoyl transferase-1 enzymatic activities, associated with an accretion of n-3 polyunsaturated fatty acids in the total composition of liver homogenate. Glucose homeostasis and plasma free fatty acid levels were improved while visceral adiposity was slightly decreased. These results confirm that the incorporation of chia seed in the diet in postnatal life may provide a viable therapeutic option for preventing/mitigating adverse outcomes induced by an SRD from utero to adulthood. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Four grams of glucose

    OpenAIRE

    Wasserman, David H.

    2008-01-01

    Four grams of glucose circulates in the blood of a person weighing 70 kg. This glucose is critical for normal function in many cell types. In accordance with the importance of these 4 g of glucose, a sophisticated control system is in place to maintain blood glucose constant. Our focus has been on the mechanisms by which the flux of glucose from liver to blood and from blood to skeletal muscle is regulated. The body has a remarkable capacity to satisfy the nutritional need for glucose, while ...

  18. Neonatal hypothyroidism affects testicular glucose homeostasis through increased oxidative stress in prepubertal mice: effects on GLUT3, GLUT8 and Cx43.

    Science.gov (United States)

    Sarkar, D; Singh, S K

    2017-07-01

    Thyroid hormones (THs) play an important role in maintaining the link between metabolism and reproduction and the altered THs status is associated with induction of oxidative stress in various organs like brain, heart, liver and testis. Further, reactive oxygen species play a pivotal role in regulation of glucose homeostasis in several organs, and glucose utilization by Leydig cells is essential for testosterone biosynthesis and thus is largely dependent on glucose transporter 8 (GLUT8). Glucose uptake by Sertoli cells is mediated through glucose transporter 3 (GLUT3) under the influence of THs to meet energy requirement of developing germ cells. THs also modulate level of gap junctional protein such as connexin 43 (Cx43), a potential regulator of cell proliferation and apoptosis in the seminiferous epithelium. Although the role of transient neonatal hypothyroidism in adult testis in terms of testosterone production is well documented, the effect of THs deficiency in early developmental period and its role in testicular glucose homeostasis and oxidative stress with reference to Cx43 in immature mice remain unknown. Therefore, the present study was conducted to evaluate the effect of neonatal hypothyroidism on testicular glucose homeostasis and oxidative stress at postnatal days (PND) 21 and 28 in relation to GLUT3, GLUT8 and Cx43. Hypothyroidism induced by 6-propyl-2-thiouracil (PTU) markedly decreased testicular glucose level with considerable reduction in expression level of GLUT3 and GLUT8. Likewise, lactate dehydrogenase (LDH) activity and intratesticular concentration of lactate were also decreased in hypothyroid mice. There was also a rise in germ cell apoptosis with increased expression of caspase-3 in PTU-treated mice. Further, neonatal hypothyroidism affected germ cell proliferation with decreased expression of proliferating cell nuclear antigen (PCNA) and Cx43. In conclusion, our results suggest that neonatal hypothyroidism alters testicular glucose

  19. Protein Kinase A Activation Promotes Cancer Cell Resistance to Glucose Starvation and Anoikis.

    Directory of Open Access Journals (Sweden)

    Roberta Palorini

    2016-03-01

    Full Text Available Cancer cells often rely on glycolysis to obtain energy and support anabolic growth. Several studies showed that glycolytic cells are susceptible to cell death when subjected to low glucose availability or to lack of glucose. However, some cancer cells, including glycolytic ones, can efficiently acquire higher tolerance to glucose depletion, leading to their survival and aggressiveness. Although increased resistance to glucose starvation has been shown to be a consequence of signaling pathways and compensatory metabolic routes activation, the full repertoire of the underlying molecular alterations remain elusive. Using omics and computational analyses, we found that cyclic adenosine monophosphate-Protein Kinase A (cAMP-PKA axis activation is fundamental for cancer cell resistance to glucose starvation and anoikis. Notably, here we show that such a PKA-dependent survival is mediated by parallel activation of autophagy and glutamine utilization that in concert concur to attenuate the endoplasmic reticulum (ER stress and to sustain cell anabolism. Indeed, the inhibition of PKA-mediated autophagy or glutamine metabolism increased the level of cell death, suggesting that the induction of autophagy and metabolic rewiring by PKA is important for cancer cellular survival under glucose starvation. Importantly, both processes actively participate to cancer cell survival mediated by suspension-activated PKA as well. In addition we identify also a PKA/Src mechanism capable to protect cancer cells from anoikis. Our results reveal for the first time the role of the versatile PKA in cancer cells survival under chronic glucose starvation and anoikis and may be a novel potential target for cancer treatment.

  20. Microbial production of glucose/fructose syrups

    Energy Technology Data Exchange (ETDEWEB)

    Matur, A.; Saglam, N.

    1982-04-01

    With the ever-increasing demand for sugar and the trend in rising price, rapid progress in research on new and/or alternative sweeteners has been inevitable during the past decade or so. Pure glucose, glucose/fructose, glucose/maltose syrups are often called isosyrups. Isosyrups have been recognized as a good alternative sources of sugar. These are used today in the manufacture of soft drinks, jams and jellies, confectionary, baking fermentation, dietetic and infant food, ice-cream, pharmaceutical processes, etc. Isosyrups are produced by hydrolysis of starch and cellulocis raw materials have been utilized for the production of isosyrups.

  1. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Español Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical term for high blood glucose (blood sugar). High ... We Are Research Leaders We Support Your Doctor Student Resources Patient Access to Research Research Resources Practice ...

  2. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Español Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical term for high blood glucose (blood sugar). High ... Type 2 Diabetes program to get help and support during your first year. Featured Book Type 2 ...

  3. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... and eAG Hypoglycemia (Low blood glucose) Hyperglycemia (High blood glucose) Dawn Phenomenon Checking for Ketones Tight Diabetes Control donate en -- A Future Without Diabetes - a-future- ...

  4. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day ... DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing ...

  5. Glucose-6-phosphate dehydrogenase

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003671.htm Glucose-6-phosphate dehydrogenase test To use the sharing features on this page, please enable JavaScript. Glucose-6-phosphate dehydrogenase (G6PD) is a protein that ...

  6. Glucose test (image)

    Science.gov (United States)

    ... person with diabetes constantly manages their blood's sugar (glucose) levels. After a blood sample is taken and tested, it is determined whether the glucose levels are low or high. Following your health ...

  7. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... symptoms include the following: High blood glucose High levels of sugar in the urine Frequent urination Increased ... you should check and what your blood glucose levels should be. Checking your blood and then treating ...

  8. [Blood glucose self monitoring].

    Science.gov (United States)

    Wascher, Thomas C; Stechemesser, Lars

    2016-04-01

    Self monitoring of blood glucose contributes to the integrated management of diabetes mellitus. It, thus, should be available for all patients with diabetes mellitus type-1 and type-2. Self monitoring of blood glucose improves patients safety, quality of life and glucose control. The current article represents the recommendations of the Austrian Diabetes Association for the use of blood glucose self monitoring according to current scientific evidence.

  9. Effects of Thyroidectomy and Thyroxine on Glucose Transport ...

    African Journals Online (AJOL)

    Thyroid hormone has been known to alter glucose metabolism. This study was conducted to investigate the effect of thyroidectomy and thyroxine on glucose transport in the small intestine. Forty rats were randomly selected into four groups of ten rats. Groups one and two rats were thyroidectomised to make them ...

  10. Effect of ghrelin on glucose regulation in mice

    Science.gov (United States)

    Improvement of glucose metabolism after bariatric surgery appears to be from the composite effect of the alterations in multiple circulating gut hormone concentrations. However, their individual effect on glucose metabolism during different conditions is not clear. The objective of this study was to...

  11. Glucose Alters Per2 Rhythmicity Independent of AMPK, Whereas AMPK Inhibitor Compound C Causes Profound Repression of Clock Genes and AgRP in mHypoE-37 Hypothalamic Neurons

    NARCIS (Netherlands)

    Oosterman, Johanneke E.; Belsham, Denise D.

    2016-01-01

    Specific neurons in the hypothalamus are regulated by peripheral hormones and nutrients to maintain proper metabolic control. It is unclear if nutrients can directly control clock gene expression. We have therefore utilized the immortalized, hypothalamic cell line mHypoE-37, which exhibits robust

  12. Altered metabolism in cancer

    Directory of Open Access Journals (Sweden)

    Locasale Jason W

    2010-06-01

    Full Text Available Abstract Cancer cells have different metabolic requirements from their normal counterparts. Understanding the consequences of this differential metabolism requires a detailed understanding of glucose metabolism and its relation to energy production in cancer cells. A recent study in BMC Systems Biology by Vasquez et al. developed a mathematical model to assess some features of this altered metabolism. Here, we take a broader look at the regulation of energy metabolism in cancer cells, considering their anabolic as well as catabolic needs. See research article: http://www.biomedcentral.com/1752-0509/4/58/

  13. Glucose screening tests during pregnancy

    Science.gov (United States)

    Oral glucose tolerance test - pregnancy; OGTT - pregnancy; Glucose challenge test - pregnancy; Gestational diabetes - glucose screening ... During the first step, you will have a glucose screening test: You DO NOT need to prepare ...

  14. 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.

  15. Nitrogenous compounds stimulate glucose-derived acid production by oral Streptococcus and Actinomyces.

    Science.gov (United States)

    Norimatsu, Yuka; Kawashima, Junko; Takano-Yamamoto, Teruko; Takahashi, Nobuhiro

    2015-09-01

    Both Streptococcus and Actinomyces can produce acids from dietary sugars and are frequently found in caries lesions. In the oral cavity, nitrogenous compounds, such as peptides and amino acids, are provided continuously by saliva and crevicular gingival fluid. Given that these bacteria can also utilize nitrogen compounds for their growth, it was hypothesized that nitrogenous compounds may influence their acid production; however, no previous studies have examined this topic. Therefore, the present study aimed to assess the effects of nitrogenous compounds (tryptone and glutamate) on glucose-derived acid production by Streptococcus and Actinomyces. Acid production was evaluated using a pH-stat method under anaerobic conditions, whereas the amounts of metabolic end-products were quantified using high performance liquid chromatography. Tryptone enhanced glucose-derived acid production by up to 2.68-fold, whereas glutamate enhanced Streptococcus species only. However, neither tryptone nor glutamate altered the end-product profiles, indicating that the nitrogenous compounds stimulate the whole metabolic pathways involving in acid production from glucose, but are not actively metabolized, nor do they alter metabolic pathways. These results suggest that nitrogenous compounds in the oral cavity promote acid production by Streptococcus and Actinomyces in vivo. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

  16. Impaired embryonic development in glucose-6-phosphate dehydrogenase-deficient Caenorhabditis elegans due to abnormal redox homeostasis induced activation of calcium-independent phospholipase and alteration of glycerophospholipid metabolism.

    Science.gov (United States)

    Chen, Tzu-Ling; Yang, Hung-Chi; Hung, Cheng-Yu; Ou, Meng-Hsin; Pan, Yi-Yun; Cheng, Mei-Ling; Stern, Arnold; Lo, Szecheng J; Chiu, Daniel Tsun-Yee

    2017-01-12

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a commonly pervasive inherited disease in many parts of the world. The complete lack of G6PD activity in a mouse model causes embryonic lethality. The G6PD-deficient Caenorhabditis elegans model also shows embryonic death as indicated by a severe hatching defect. Although increased oxidative stress has been implicated in both cases as the underlying cause, the exact mechanism has not been clearly delineated. In this study with C. elegans, membrane-associated defects, including enhanced permeability, defective polarity and cytokinesis, were found in G6PD-deficient embryos. The membrane-associated abnormalities were accompanied by impaired eggshell structure as evidenced by a transmission electron microscopic study. Such loss of membrane structural integrity was associated with abnormal lipid composition as lipidomic analysis revealed that lysoglycerophospholipids were significantly increased in G6PD-deficient embryos. Abnormal glycerophospholipid metabolism leading to defective embryonic development could be attributed to the increased activity of calcium-independent phospholipase A 2 (iPLA) in G6PD-deficient embryos. This notion is further supported by the fact that the suppression of multiple iPLAs by genetic manipulation partially rescued the embryonic defects in G6PD-deficient embryos. In addition, G6PD deficiency induced disruption of redox balance as manifested by diminished NADPH and elevated lipid peroxidation in embryos. Taken together, disrupted lipid metabolism due to abnormal redox homeostasis is a major factor contributing to abnormal embryonic development in G6PD-deficient C. elegans.

  17. Glucose cycling in islets from healthy and diabetic rats

    International Nuclear Information System (INIS)

    Khan, A.; Chandramouli, V.; Ostenson, C.G.; Loew, H.L.; Landau, B.R.; Efendic, S.

    1990-01-01

    Pancreatic islets from healthy (control) and neonatally streptozocin-induced diabetic (STZ-D) rats, a model for non-insulin-dependent diabetes mellitus, were incubated with 3 H 2 O and 5.5 or 16.7 mM glucose. At 5.5 mM glucose, no detectable [ 3 H]glucose was formed. At 16.7 mM, 2.2 patom.islet-1.h-1 of 3 H was incorporated into glucose by the control islets and 5.4 patom.islet-1.h-1 by STZ-D islets. About 75% of the 3 H was bound to carbon-2 of the glucose. Glucose utilization was 35.3 pmol.islet-1.h-1 by the control and 19.0 pmol.islet-1.h-1 by the STZ-D islets. Therefore, 4.5% of the glucose-6-phosphate formed by the control islets and 15.7% by the STZ-D islets was dephosphorylated. This presumably occurred in the beta-cells of the islets catalyzed by glucose-6-phosphatase. An increased glucose cycling, i.e., glucose----glucose-6-phosphate----glucose, in islets of STZ-D rats may contribute to the decreased insulin secretion found in these animals

  18. Critical Care Glucose Point-of-Care Testing.

    Science.gov (United States)

    Narla, S N; Jones, M; Hermayer, K L; Zhu, Y

    Maintaining blood glucose concentration within an acceptable range is a goal for patients with diabetes mellitus. Point-of-care glucose meters initially designed for home self-monitoring in patients with diabetes have been widely used in the hospital settings because of ease of use and quick reporting of blood glucose information. They are not only utilized for the general inpatient population but also for critically ill patients. Many factors affect the accuracy of point-of-care glucose testing, particularly in critical care settings. Inaccurate blood glucose information can result in unsafe insulin delivery which causes poor glucose control and can be fatal. Healthcare professionals should be aware of the limitations of point-of-care glucose testing. This chapter will first introduce glucose regulation in diabetes mellitus, hyperglycemia/hypoglycemia in the intensive care unit, importance of glucose control in critical care patients, and pathophysiological variables of critically ill patients that affect the accuracy of point-of-care glucose testing. Then, we will discuss currently available point-of-care glucose meters and preanalytical, analytical, and postanalytical sources of variation and error in point-of-care glucose testing. © 2016 Elsevier Inc. All rights reserved.

  19. 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.

  20. Peripheral glucose levels and cognitive outcome after ischemic stroke : Results from the Munich Stroke Cohort

    NARCIS (Netherlands)

    Zietemann, Vera; Wollenweber, Frank Arne; Bayer-Karpinska, Anna; Biessels, Geert Jan; Dichgans, Martin

    2016-01-01

    Introduction: The relationship between glucose metabolism and stroke outcome is likely to be complex. We examined whether there is a linear or non-linear relationship between glucose measures in the acute phase of stroke and post-stroke cognition, and whether altered glucose metabolism at different

  1. Measuring brain glucose phosphorylation with labeled glucose

    International Nuclear Information System (INIS)

    Brondsted, H.E.; Gjedde, A.

    1988-01-01

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

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

    Directory of Open Access Journals (Sweden)

    June Zhou

    2017-09-01

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

  3. Insulin secretion and cellular glucose metabolism after prolonged low-grade intralipid infusion in young men

    DEFF Research Database (Denmark)

    Jensen, Christine B; Storgaard, Heidi; Holst, Jens Juul

    2003-01-01

    We examined the simultaneous effects of a 24-h low-grade Intralipid infusion on peripheral glucose disposal, intracellular glucose partitioning and insulin secretion rates in twenty young men, by 2-step hyperinsulinemic euglycemic clamp [low insulin clamp (LI), 10 mU/m(2) x min; high insulin clamp...... Intralipid infusion. At LI, glucose oxidation decreased by 10%, whereas glucose disposal, glycolytic flux, glucose storage, and glucose production were not significantly altered. At HI, glucose disposal, and glucose oxidation decreased by 12% and 24%, respectively, during Intralipid infusion. Glycolytic flux......, glucose storage, and glucose production were unchanged. Insulin secretion rates increased in response to Intralipid infusion, but disposition indices (DI = insulin action.insulin secretion) were unchanged. In conclusion, a 24-h low-grade Intralipid infusion caused insulin resistance in the oxidative (but...

  4. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Complications Neuropathy Foot Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing ...

  5. Biostable glucose permeable polymer

    DEFF Research Database (Denmark)

    2017-01-01

    A new biostable glucose permeable polymer has been developed which is useful, for example, in implantable glucose sensors. This biostable glucose permeable polymer has a number of advantageous characteristics and, for example, does not undergo hydrolytic cleavage and degradation, thereby providing...... a composition that facilitates long term sensor stability in vivo. The versatile characteristics of this polymer allow it to be used in a variety of contexts, for example to form the body of an implantable glucose sensor. The invention includes the polymer composition, sensor systems formed from this polymer...

  6. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Complications Neuropathy Foot Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More ...

  7. Oral Glucose Tolerance Test Revisted | Mshelia | Nigerian Journal of ...

    African Journals Online (AJOL)

    Objective: The present review was undertaken to create the required utilization of oral glucose tolerance test in a developing country with a high prevalence of diabetes mellitus and its complications. Sources of data: This review is primarily based on available literature on local and international studies on oral glucose ...

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

    DEFF Research Database (Denmark)

    Jensen, Thomas Elbenhardt; Richter, Erik

    2012-01-01

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

  9. Glucose as substrate and signal in priming: Results from experiments with non-metabolizable glucose analogues

    Science.gov (United States)

    Mason-Jones, Kyle; Kuzyakov, Yakov

    2016-04-01

    Priming of soil organic matter remains the subject of intense research, but a mechanistic explanation of the phenomenon remains to be demonstrated. This is largely due to the multiple effects of easily available carbon on the soil microbial community, and the challenge of separating these influences from one another. Several glucose analogues can be taken up by microbial glucose transporters and have similar regulatory effects on metabolism. These substances are, however, not easily catabolized by the common glycolytic pathway, limiting their energy value. Therefore, they can be used to distinguish between the action of glucose as a metabolic signal, and its influence as an energy source. We incubated an agricultural Haplic Luvisol under controlled conditions for 24 days after addition of: 1) glucose, 2) 3-O-methyl-glucose, 3) α-methylglucoside or 4) 2-deoxyglucose, at three concentration levels, along with a control treatment of water addition. CO2 efflux from soil was monitored by trapping evolved CO2 in NaOH and back-titration with HCl. On the first day after amendment, CO2 efflux from soil increased strongly for glucose and much less for the analogues, relative to the control. Only glucose caused a peak in efflux within the first two days. Peak mineralization of 2-deoxyglucose and α-methylglucoside was delayed until the third day, while CO2 from 3-O-methyl-glucose increased gradually, with a peak delayed by approximately a week. For glucose, the immediate increase in respiration was strongly dependent on the amount of glucose added, but this was not the case for the analogues, indicating that the catabolic potential for these substances was saturated. This is consistent with only a small part of the microbial community being capable of utilizing these carbon sources. In a subsequent experiment, 14C-labelled glucose or 14C-labelled 3-O-methyl-glucose were added to the same soil, enabling quantification of the priming effect. For 3-O-methyl-glucose, priming was

  10. Moderate glucose supply reduces hemolysis during systemic inflammation

    Directory of Open Access Journals (Sweden)

    Jägers J

    2018-03-01

    Full Text Available Johannes Jägers,1 Stephan Brauckmann,2 Michael Kirsch,1 Katharina Effenberger-Neidnicht1,3 1Institute of Physiological Chemistry, University Hospital Essen, Essen, Germany; 2Clinic for Anesthesiology and Intensive Care, University Hospital Essen, Essen, Germany; 3Institute of Physiological Chemistry, University Hospital Essen, Essen, Germany Background: Systemic inflammation alters energy metabolism. A sufficient glucose level, however, is most important for erythrocytes, since erythrocytes rely on glucose as sole source of energy. Damage to erythrocytes leads to hemolysis. Both disorders of glucose metabolism and hemolysis are associated with an increased risk of death. The objective of the study was to investigate the impact of intravenous glucose on hemolysis during systemic inflammation.Materials and methods: Systemic inflammation was accomplished in male Wistar rats by continuous lipopolysaccharide (LPS infusion (1 mg LPS/kg and h, 300 min. Sham control group rats received Ringer’s solution. Glucose was supplied moderately (70 mg glucose/kg and h or excessively (210 mg glucose/kg and h during systemic inflammation. Vital parameters (eg, systemic blood pressure as well as blood and plasma parameters (eg, concentrations of glucose, lactate and cell-free hemoglobin, and activity of lactate dehydrogenase were measured hourly. Clot formation was analyzed by thromboelastometry.Results: Continuous infusion of LPS led to a so-called post-aggression syndrome with disturbed electrolyte homeostasis (hypocalcemia, hyperkalemia, and hypernatremia, changes in hemodynamics (tachycardia and hypertension, and a catabolic metabolism (early hyperglycemia, late hypoglycemia, and lactate formation. It induced severe tissue injury (significant increases in plasma concentrations of transaminases and lactate dehydrogenase, alterations in blood coagulation (disturbed clot formation, and massive hemolysis. Both moderate and excessive glucose supply reduced LPS

  11. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Your Carbs Count Glycemic Index Low-Calorie Sweeteners Sugar and Desserts Fitness Exercise & Type 1 Diabetes Get Started Safely Get And Stay Fit Types ... the following: High blood glucose High levels of sugar in the ... Part of managing your diabetes is checking your blood glucose often. Ask your ...

  12. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... by Mail Close www.diabetes.org > Living With Diabetes > Treatment and Care > Blood Glucose Testing Share: Print Page ... and-how-tos, . In this section Living With Diabetes Treatment and Care Blood Glucose Testing Checking Your Blood ...

  13. Blood Test: Glucose

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Blood Test: Glucose KidsHealth / For Parents / Blood Test: Glucose What's ... español Análisis de sangre: glucosa What Is a Blood Test? A blood test is when a sample of ...

  14. 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...

  15. The Negative Influence of High-Glucose Ambience on Neurogenesis in Developing Quail Embryos

    OpenAIRE

    Chen, Yao; Fan, Jian-xia; Zhang, Zhao-long; Wang, Guang; Cheng, Xin; Chuai, Manli; Lee, Kenneth Ka Ho; Yang, Xuesong

    2013-01-01

    Gestational diabetes is defined as glucose intolerance during pregnancy and it is presented as high blood glucose levels during the onset pregnancy. This condition has an adverse impact on fetal development but the mechanism involved is still not fully understood. In this study, we investigated the effects of high glucose on the developing quail embryo, especially its impact on the development of the nervous system. We established that high glucose altered the central nervous system mophologi...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-06-15

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

  17. Nanomaterials in glucose sensing

    CERN Document Server

    Burugapalli, Krishna

    2013-01-01

    The smartness of nano-materials is attributed to their nanoscale and subsequently unique physicochemical properties and their use in glucose sensing has been aimed at improving performance, reducing cost and miniaturizing the sensor and its associated instrumentation. So far, portable (handheld) glucose analysers were introduced for hospital wards, emergency rooms and physicians' offices; single-use strip systems achieved nanolitre sampling for painless and accurate home glucose monitoring; advanced continuous monitoring devices having 2 to 7 days operating life are in clinical and home use; and continued research efforts are being made to develop and introduce increasingly advanced glucose monitoring systems for health as well as food, biotechnology, cell and tissue culture industries. Nanomaterials have touched every aspect of biosensor design and this chapter reviews their role in the development of advanced technologies for glucose sensing, and especially for diabetes. Research shows that overall, nanomat...

  18. Brain Glucose Metabolism Controls Hepatic Glucose and Lipid Production

    OpenAIRE

    Lam, Tony K.T.

    2007-01-01

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

  19. Resolving futile glucose cycling and glycogenolytic contributions to plasma glucose levels following a glucose load

    NARCIS (Netherlands)

    Nunes, P.M.; Jarak, I.; Heerschap, A.; Jones, J.G.

    2014-01-01

    PURPOSE: After a glucose load, futile glucose/glucose-6-phosphate (G6P) cycling (FGC) generates [2-(2) H]glucose from (2) H2 O thereby mimicking a paradoxical glycogenolytic contribution to plasma glucose levels. Contributions of load and G6P derived from gluconeogenesis, FGC, and glycogenolysis to

  20. Enhanced muscle glucose metabolism after exercise

    DEFF Research Database (Denmark)

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

    1984-01-01

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

  1. Exogenous amino acids suppress glucose oxidation and potentiate hepatic glucose production in late gestation fetal sheep.

    Science.gov (United States)

    Brown, Laura D; Kohn, Jaden R; Rozance, Paul J; Hay, William W; Wesolowski, Stephanie R

    2017-05-01

    Acute amino acid (AA) infusion increases AA oxidation rates in normal late gestation fetal sheep. Because the fetal oxygen consumption rate does not change with increased AA oxidation, we hypothesized that AA infusion would suppress glucose oxidation pathways and that the additional carbon supply from AA would activate hepatic glucose production. To test this, late gestation fetal sheep were infused intravenously for 3 h with saline or exogenous AA (AA). Glucose tracer metabolic studies were performed and skeletal muscle and liver tissues samples were collected. AA infusion increased fetal arterial plasma branched chain AA, cortisol, and glucagon concentrations. Fetal glucose utilization rates were similar between basal and AA periods, yet the fraction of glucose oxidized and the glucose oxidation rate were decreased by 40% in the AA period. AA infusion increased expression of PDK4 , an inhibitor of glucose oxidation, nearly twofold in muscle and liver. In liver, AA infusion tended to increase PCK1 gluconeogenic gene and PCK1 correlated with plasma cortisol concentrations. AA infusion also increased liver mRNA expression of the lactate transporter gene ( MCT1) , protein expression of GLUT2 and LDHA, and phosphorylation of AMPK, 4EBP1, and S6 proteins. In isolated fetal hepatocytes, AA supplementation increased glucose production and PCK1 , LDHA , and MCT1 gene expression. These results demonstrate that AA infusion into fetal sheep competitively suppresses glucose oxidation and potentiates hepatic glucose production. These metabolic patterns support flexibility in fetal metabolism in response to increased nutrient substrate supply while maintaining a relatively stable rate of oxidative metabolism. Copyright © 2017 the American Physiological Society.

  2. Muscle glucose metabolism following exercise in the rat

    DEFF Research Database (Denmark)

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

    1982-01-01

    Muscle glycogen stores are depleted during exercise and are rapidly repleted during the recovery period. To investigate the mechanism for this phenomenon, untrained male rats were run for 45 min on a motor-driven treadmill and the ability of their muscles to utilize glucose was then assessed during...... in glucose utilization enhanced by prior exercise appeared to be glucose transport across the cell membrane, as in neither control nor exercised rats did free glucose accumulate in the muscle cell. Following exercise, the ability of insulin to stimulate the release of lactate into the perfusate was unaltered......; however its ability to stimulate the incorporation of [(14)C]glucose into glycogen in certain muscles was enhanced. Thus at a concentration of 75 muU/ml insulin stimulated glycogen synthesis eightfold more in the fast-twitch red fibers of the red gastrocnemius than it did in the same muscle...

  3. Implanted electroenzymatic glucose sensors.

    Science.gov (United States)

    Clark, L C; Duggan, C A

    1982-01-01

    The advent of electrochemical sensors for intermittent sampling of blood gases and hydrogen ions in the clinic, intensive care, and surgical units has revolutionized diagnostic and critical care medical technics. The use of electrochemical sensors for continuous transcutaneous monitoring of blood gases is further enhancing the medical surveillance of patients. The more recent introduction of glucose and other electroenzymatic sensors has stimulated broad research in the development of metabolic monitoring. For the present research, the glucose sensor widely used for the rapid specific micro-analysis of whole blood and plasma is explored for possible use as an in vivo intravascular or tissue-implanted sensor. This sensor is based on the polarographic measurement of hydrogen peroxide generated by glucose oxidase (EC 1.1.3.4) held between two membranes. The first membrane allows the diffusion of glucose, ions, and many other small molecules, while the second membrane allows the diffusion of the glucose-generated hydrogen peroxide to the platinum surface, but excludes ascorbic acid, bilirubin, and uric acid. Such sensors respond rapidly and specifically when acutely implanted subcutaneously in cats and dogs. They function well as glucose-sensor-tipped venous catheters. One sensor was repeatedly used for in vitro polarograms, subcutaneous and blood glucose monitoring, over a period of ten months, with storage in the cold between uses, with the complete retention of its response characteristics.

  4. Pareto utility

    NARCIS (Netherlands)

    Ikefuji, M.; Laeven, R.J.A.; Magnus, J.R.; Muris, C.H.M.

    2013-01-01

    In searching for an appropriate utility function in the expected utility framework, we formulate four properties that we want the utility function to satisfy. We conduct a search for such a function, and we identify Pareto utility as a function satisfying all four desired properties. Pareto utility

  5. The diabetic heart utilizes ketone bodies as an energy source.

    Science.gov (United States)

    Mizuno, Yuji; Harada, Eisaku; Nakagawa, Hitoshi; Morikawa, Yoshinobu; Shono, Makoto; Kugimiya, Fumihito; Yoshimura, Michihiro; Yasue, Hirofumi

    2017-12-01

    Diabetic heart is characterized by failure of insulin to increase glucose uptake and increasingly relies on free fatty acids (FFAs) as a source of fuel in animal models. However, it is not well known how cardiac energy metabolism is altered in diabetic hearts in humans. We examined cardiac fuel metabolism in the diabetics as compared to non-diabetics who underwent cardiac catheterization for heart diseases. The study subjects comprised 81 patients (male 55, female 26, average age 63.0±10.0years) who underwent the cardiac catheterization for heart diseases. Thirty-six patients were diagnosed as diabetics (diabetic group) and 45 as non-diabetics (non-diabetic group). Blood samplings were done in both the aortic root (Ao) and coronary sinus (CS) simultaneously and the plasma levels of FFAs, glucose, lactate, pyruvate, total ketone bodies and β-hydroxybutyrate were measured and compared between the two groups. The myocardial uptake of glucose, lactate and pyruvate were decreased, whereas those of total ketone bodies, β-hydroxybutyrate and acetoacetate were increased in the diabetics as compared to the non-diabetics. However, the myocardial uptakes of FFAs were not significantly increased in the diabetics as compared to the non-diabetics. Cardiac uptakes of carbohydrate (glucose, lactate and pyruvate) were decreased, whereas those of total ketone bodies and β-hydroxybutyrate were increased in the diabetics as compared to the non-diabetics in humans. Ketone bodies therefore are utilized as an energy source partially replacing glucose in the human diabetic heart. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. Blood Glucose Determination

    DEFF Research Database (Denmark)

    Lippi, Giuseppe; Nybo, Mads; Cadamuro, Janne

    2018-01-01

    The measurement of fasting plasma glucose may be biased by a time-dependent decrease of glucose in blood tubes, mainly attributable to blood cell metabolism when glycolysis is not rapidly inhibited or blood cells cannot be rapidly separated from plasma. Although glycolysis inhibitors such as sodium...... fluoride (NaF) in combination with potassium oxalate (KOx) are currently used for overcoming this drawback, their efficacy for stabilizing blood glucose is seemingly limited, and probably lower than that of newer additives such as the citrate buffer. Therefore, we performed a critical analysis...

  7. Novel oxolane derivative DMTD mitigates high glucose-induced erythrocyte apoptosis by regulating oxidative stress.

    Science.gov (United States)

    Jagadish, Swamy; Hemshekhar, Mahadevappa; NaveenKumar, Somanathapura K; Sharath Kumar, Kothanahally S; Sundaram, Mahalingam S; Basappa; Girish, Kesturu S; Rangappa, Kanchugarakoppal S

    2017-11-01

    Chronic hyperglycemia is one of the characteristic conditions associated with Diabetes Mellitus (DM), which often exerts deleterious effects on erythrocyte morphology and hemodynamic properties leading to anemia and diabetes-associated vascular complications. High glucose-induced over production of reactive oxygen species (ROS) can alter the blood cell metabolism and biochemical functions subsequently causing eryptosis (red blood cell death), yet another complication of concern in DM. Therefore, blocking high glucose-induced oxidative damage and subsequent eryptosis is of high importance in the better management of DM and associated vascular complications. In this study, we synthesized an oxolane derivative 1-(2,2-dimethyltetrahydrofuro[2,3][1,3]dioxol-5-yl)ethane-1,2-diol (DMTD), and demonstrated its efficacy to mitigate hyperglycemia-induced ROS generation and subsequent eryptosis. We showed that DMTD effectively inhibits high glucose-induced ROS generation, intracellular calcium levels, phosphaditylserine (PS) scrambling, calpain and band 3 activation, LDH leakage, protein glycation and lipid peroxidation, meanwhile enhances the antioxidant indices, osmotic fragility and Na + /K + -ATPase activity in erythrocytes. DMTD dose dependently decreased the glycated hemoglobin level and enhances the glucose utilization by erythrocytes in vitro. Further, DMTD alleviated the increase in ROS production, intracellular Ca 2+ level and PS externalization in the erythrocytes of human diabetic subjects and enhanced the Na + /K + -ATPase activity. Taken together, the synthesized oxolane derivative DMTD could be a novel synthetic inhibitor of high glucose-induced oxidative stress and eryptosis. Considering the present results DMTD could be a potential therapeutic to treat DM and associated complications and open new avenues in developing synthetic therapeutic targeting of DM-associated complications. Copyright © 2017. Published by Elsevier Inc.

  8. Alterações clínicolaboratoriais em pacientes com malária por Plasmodium vivax e deficiência de glicose-6-fosfato desidrogenase tratados com 0,50mg/kg/dia de primaquina Clinical and laboratorial alterations in Plasmodium vivax malaria patients and glucose-6-phosphate dehydrogenase deficiency treated with primaquine at 0.50mg/kg/day

    Directory of Open Access Journals (Sweden)

    Mônica C.M. Silva

    2004-06-01

    Full Text Available O efeito adverso da primaquina na dose de 0,50mg/kg/dia foi investigado em onze pacientes com malária vivax (três com deficiência de glicose-6-fosfato desidrogenase. Alterações clínicas e laboratoriais indicaram hemólise aguda apenas nos enzimopênicos, o que fez com que o tratamento fosse interrompido. Nossos resultados sugerem a necessidade do emprego de um teste de triagem para a deficiência de G6PD em áreas endêmicas de malária vivax a fim de se evitar complicações causadas pelo uso da primaquina.The adverse effects of primaquine (0.50mg/kg/day were investigated in eleven patients with vivax malaria (three patients with glucose-6-phosphate dehydrogenase deficiency. Clinical and laboratorial alterations indicated acute hemolysis in only the enzymopenic patients and treatment was interrupted. Our results suggest that screening for G6PD deficiency should be carried out in patients with vivax malaria infection in order to avoid complications due to primaquine.

  9. 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

  10. Hyperglycemia (High Blood Glucose)

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  1. Glucose control in mobile type 1 (insulin-dependent) diabetic patients by means of a semi-automatic feedback controlled insulin infusion system.

    Science.gov (United States)

    Piwernetz, K; Renner, R; Hepp, K D

    1982-09-01

    A portable insulin dosing device (Siemens) was used together with a programmable pocket calculator and a glucose analyzer for short-term adaptation of continuous intravenous insulin infusion to blood glucose alterations. A special algorithm was developed which utilizes a given blood glucose value and the glucose rate of change obtained from two to four consecutive samples as input variables. In contrast to current techniques of feedback-regulation, which require continuous glucose monitoring, intermittent blood sampling allows greater mobility of patients. With the semi-automatic feedback system, euglycaemic control was obtained for 12-h periods in ten Type 1 (insulin-dependent) diabetic patients (maximum value 9.50 mmol/l, minimum value 2.83 mmol/l). Severe hypoglycaemia occurred in no case and additional control by glucose infusion appeared to be unnecessary. Light exercise after termination of insulin dose for standard meals led to glycaemic excursions with a rapid decrease (mean 1.08 +/- 0.09 mmol/l), followed by a rebound (0.59 +/- 0.07 mmol/l) in each patient. The amplitude of these excursions decreased with increasing distance from the peak of the meal dose. Comparison of feedback-control alone with feedback by glucose plus preprogrammed dose (4 U/h) at the onset of the test meal revealed lower post-prandial glucose levels (post-prandial maximum +/- SEM: 6.49 +/- 0.18 versus 7.71 +/- 0.79 mmol/l) and a lower infusion rate of insulin for the combined regimen (mean post-prandial maximum +/- SEM: 8.4 +/- 1.2 versus 12.0 +/- 0 IU/h). The system is useful for programming of portable infusion devices and studies based on euglycaemic control in unrestrained patients.

  2. Monitoring and management of lung cancer patients following curative-intent treatment: clinical utility of 2-deoxy-2-[fluorine-18]fluoro-d-glucose positron emission tomography/computed tomography

    Directory of Open Access Journals (Sweden)

    Sawada S

    2016-04-01

    Full Text Available Shigeki Sawada, Hiroshi Suehisa, Tsuyoshi Ueno, Ryujiro Sugimoto, Motohiro Yamashita Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan Abstract: A large number of studies have demonstrated that 2-deoxy-2-[fluorine-18]fluoro-d-glucose positron emission tomography/computed tomography (FDG-PET/CT is superior to conventional modalities for the diagnosis of lung cancer and the evaluation of the extent of the disease. However, the efficacy of PET/CT in a follow-up surveillance setting following curative-intent treatments for lung cancer has not yet been established. We reviewed previous papers and evaluated the potential efficacy of PET-CT in the setting of follow-up surveillance. The following are our findings: 1 PET/CT is considered to be superior or equivalent to conventional modalities for the detection of local recurrence. However, inflammatory changes and fibrosis after treatments in local areas often result in false-positive findings; 2 the detection of asymptomatic distant metastasis is considered to be an advantage of PET/CT in a follow-up setting. However, it should be noted that detection of brain metastasis with PET/CT has some limitation, similar to its use in pretreatment staging; 3 additional radiation exposure and higher medical cost arising from the use of PET/CT should be taken into consideration, particularly in patients who might not have cancer after curative-intent treatment and are expected to have a long lifespan. The absence of any data regarding survival benefits and/or improvements in quality of life is another critical issue. In summary, PET/CT is considered to be more accurate and sensitive than conventional modalities for the detection of asymptomatic recurrence after curative-intent treatments. These advantages could modify subsequent management in patients with suspected recurrence and might contribute to the selection of appropriate treatments for recurrence

  3. Assessment of insulin action in insulin-dependent diabetes mellitus using [6(14)C]glucose, [3(3)H]glucose, and [2(3)H]glucose. Differences in the apparent pattern of insulin resistance depending on the isotope used

    International Nuclear Information System (INIS)

    Bell, P.M.; Firth, R.G.; Rizza, R.A.

    1986-01-01

    To determine whether [2(3)H], [3(3)H], and [6(14)C]glucose provide an equivalent assessment of glucose turnover in insulin-dependent diabetes mellitus (IDDM) and nondiabetic man, glucose utilization rates were measured using a simultaneous infusion of these isotopes before and during hyperinsulinemic euglycemic clamps. In the nondiabetic subjects, glucose turnover rates determined with [6(14)C]glucose during insulin infusion were lower (P less than 0.02) than those determined with [2(3)H]glucose and higher (P less than 0.01) than those determined with [3(3)H]glucose. In IDDM, glucose turnover rates measured with [6(14)C]glucose during insulin infusion were lower (P less than 0.05) than those determined with [2(3)H]glucose, but were not different from those determined with [3(3)H]glucose. All three isotopes indicated the presence of insulin resistance. However, using [3(3)H]glucose led to the erroneous conclusion that glucose utilization was not significantly decreased at high insulin concentrations in the diabetic patients. [6(14)C] and [3(3)H]glucose but not [2(3)H]glucose indicated impairment in insulin-induced suppression of glucose production. These results indicate that tritiated isotopes do not necessarily equally reflect the pattern of glucose metabolism in diabetic and nondiabetic man

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

    Science.gov (United States)

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

    2014-12-01

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

  5. Overexpression of mitochondrial sirtuins alters glycolysis and mitochondrial function in HEK293 cells.

    Directory of Open Access Journals (Sweden)

    Michelle Barbi de Moura

    Full Text Available SIRT3, SIRT4, and SIRT5 are mitochondrial deacylases that impact multiple facets of energy metabolism and mitochondrial function. SIRT3 activates several mitochondrial enzymes, SIRT4 represses its targets, and SIRT5 has been shown to both activate and repress mitochondrial enzymes. To gain insight into the relative effects of the mitochondrial sirtuins in governing mitochondrial energy metabolism, SIRT3, SIRT4, and SIRT5 overexpressing HEK293 cells were directly compared. When grown under standard cell culture conditions (25 mM glucose all three sirtuins induced increases in mitochondrial respiration, glycolysis, and glucose oxidation, but with no change in growth rate or in steady-state ATP concentration. Increased proton leak, as evidenced by oxygen consumption in the presence of oligomycin, appeared to explain much of the increase in basal oxygen utilization. Growth in 5 mM glucose normalized the elevations in basal oxygen consumption, proton leak, and glycolysis in all sirtuin over-expressing cells. While the above effects were common to all three mitochondrial sirtuins, some differences between the SIRT3, SIRT4, and SIRT5 expressing cells were noted. Only SIRT3 overexpression affected fatty acid metabolism, and only SIRT4 overexpression altered superoxide levels and mitochondrial membrane potential. We conclude that all three mitochondrial sirtuins can promote increased mitochondrial respiration and cellular metabolism. SIRT3, SIRT4, and SIRT5 appear to respond to excess glucose by inducing a coordinated increase of glycolysis and respiration, with the excess energy dissipated via proton leak.

  6. Glucose metabolism in cultured trophoblasts from human placenta

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  7. Metabolism Of C(14)-Glucose By Eurytrema Pancreaticum.

    Science.gov (United States)

    Seo, Byong Seol; Rim, Han Jong; Kim, Kwang Soo; Lee, Myung Sang; Kim, Yeong Uhn; Song, Hi Yong

    1964-12-01

    1. The glucose uptake rate by Eurytrema pancreaticum was a mean value of 16.44 +/- 2.42 micro moles/hr/g, and total CO2 production rate by the fluke averaged 5.82 +/- 0.97 micro moles/hr/g. The relative specific activity of respiratory CO2 showed a mean value of 5.75 +/- 0.84 per cent. The rate of CO2 production derived from medium C(14)-glucose was a mean of 0.33 +/- 0.10 micor-mole/hr/g. Therefore, the average value of 0.32 +/- 0.04 per cent of glucose utilized by the flukes from the medium C(14)-glucose was oxidized to respiratory CO2. 2. The tissue concentration of glycogen in E. pancreaticum was a mean of 45.50 +/- 2.18 mg/g or 4.55 +/- 0.22 %/g. But the turnover rate of glycogen pool was a mean of 0.027 +/- 0.003 %/hr or 0.009 +/- 0.002 mg/hr/g. The average value of 0.64 +/- 0.23 percent of glucose utilized by the flukes from the medium C(14)-glucose was incorporated into the glycogen. 3. These data account for that only 1 per cent of the utilized glucose by the flukes participated in furnishing the oxidation into respiratory CO2 and the synthetic process into glycogen.

  8. Role of NMDA receptors in the increase of glucose metabolism in the rat brain induced by fluorocitrate.

    Science.gov (United States)

    Hirose, Shinichiro; Umetani, Yukiko; Amitani, Misato; Hosoi, Rie; Momosaki, Sotaro; Hatazawa, Jun; Gee, Antony; Inoue, Osamu

    2007-03-30

    The effect of inhibition of glial metabolism by infusion of fluorocitrate (FC, 1 nmol/microl, 2 microl) into the right striatum of the rat brain on the glucose metabolism was studied. Significant increases in [(18)F]fluorodeoxyglucose ([(18)F]FDG) uptake (45 min) in the right cerebral cortex and striatum were observed 4h after the infusion of FC, both as determined by the tissue dissection method and autoradiography. No significant increase in the initial uptake of [(18)F]FDG (1 min) was seen in the striatum. Pretreatment with dizocilpine (MK-801), an N-methyl-d-aspartate (NMDA) receptor antagonist, reduced [(18)F]FDG uptake in not only FC infused hemisphere but also in the contralateral hemisphere (saline-infused side). The radioactivity concentrations in plasma at 1, 5 and 45 min after the [(18)F]FDG injection were not altered by MK-801. This effect of MK-801 on glucose metabolism observed in the rat brain infused with FC was different from previous reports which indicated an increase in glucose metabolism in some areas of normal rat brain. In addition, the enhancement of glucose metabolism in the striatum induced by FC was almost completely abolished by pretreatment with MK-801. In the cerebral cortex, the relative ratio of radioactivity concentration in the right hemisphere to that in the left hemisphere still remained 1.37 (tissue dissection method) or 1.55 (autoradiography), which indicated that MK-801 partially blocked the effect of FC of enhancing glucose metabolism in this region. These results indicate an important role of NMDA-mediated signal transmission on the increase of glucose utilization induced by inhibition of glial metabolism.

  9. Measurement of glucose and 2-deoxy-2-[18F]fluoro-D-glucose transport and phosphorylation rates in myocardium using dual-tracer kinetic experiments

    International Nuclear Information System (INIS)

    Huang, S.C.; Williams, B.A.; Barrio, J.R.; Nissenson, C.; Hoffman, E.J.; Phelps, M.E.; Krivokapich, J.

    1987-01-01

    To examine the use of 2-deoxy-2-[ 18 F]fluoro-D-glucose (2-FDG) as a glucose analog for measuring glucose utilization rate in myocardium, dual-tracer kinetic experiments with 2-FDG and 2-[ 3 H]glucose were performed in the perfused, isolated rabbit interventricular septum to measure simultaneously the transport and phosphorylation rates of glucose and 2-FDG. Results of the present study indicated that, in the septum, (i) the transport rate constants of 2-FDG and glucose were similar in magnitude, (ii) the phosphorylation rate constant for 2-FDG was about 60% of that of glucose, (iii) hypoxia caused an increase in phosphorylation rates of glucose and 2-FDG without affecting transport. 9 refs.; 1 figure; 3 tabs

  10. Platelet-activating factor-induced increases in glucose kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Lang, C.H.; Dobrescu, C.; Hargrove, D.M.; Bagby, G.J.; Spitzer, J.J. (Louisiana State Univ. Medical Center, New Orleans (USA))

    1988-02-01

    Platelet-activating factor (PAF) is a postulated mediator of many of the early hemodynamic effects of endotoxin. The aim of the present study was to determine whether in vivo administration of PAF could produce alterations in whole-body glucose metabolism that would mimic those seen during endotoxemia. Glucose kinetics were assessed in chronically catheterized conscious rats by the constant infusion of (6-{sup 3}H)- and (U-{sup 14}C)glucose before and for 4 h after either a bolus injection or a constant infusion of PAF. The bolus injection of PAF elevated the rate of glucose appearance (R{sub a}; 44%) for 1.5 h. The lower PAF infusion rate decreased blood pressure 11% to 104 mmHg, whereas the higher infusion rate decreased pressure 34% to 77 mmHg. Both PAF infusion rates produced elevations in plasma glucose and glucose R{sub a} throughout the 4-h infusion period in a dose-related manner. The PAF infusions also induced dose-related increases in plasma glucagon and catecholamine levels throughout the infusion period. Because the constant infusion of PAF did stimulate many of the hemodynamic and metabolic alterations produced by endotoxin, this study provides additional support for the potential importance of PAF as a mediator of the early hemodynamic and metabolic sequela of endotoxin shock. Furthermore, the PAF-induced changes in glucose metabolism appear to be mediated by the resultant elevation in plasma catecholamines.

  11. Alcohol Fermentation and Biomass formation from xylose, glucose ...

    African Journals Online (AJOL)

    Cerevisiae (LB-7) was the slowest in growth and utilization of xylose into biomass (economic conversion coefficient of 0.03), while K3 showed fastest utilization of xylose (coefficient 0.76). For the production of ethanol, the fastest growth and assimilation of glucose was recorded by Pa. tannophilus (P1) (coefficient 0.56) ...

  12. Prehospital Glucose Testing for Children with Seizures: A Proposed Change in Management.

    Science.gov (United States)

    Remick, Katherine; Redgate, Christopher; Ostermayer, Daniel; Kaji, Amy H; Gausche-Hill, Marianne

    2017-01-01

    Many Emergency Medicine Services (EMS) protocols require point-of-care blood glucose testing (BGT) for any pediatric patient who presents with seizure or altered level of conscious. Few data describe the diagnostic yield of BGT when performed on all pediatric seizures regardless of presenting mental status. We analyzed a large single center dataset of pediatric patients presenting with prehospital seizures to determine the prevalence of hypoglycemic seizures and the utility of repeat BGT in the emergency department (ED). This was a retrospective, IRB-approved chart analysis of all pediatric patients (≤14 years) transported by EMS to the Harbor-UCLA pediatric ED over a 2-year period with a chief complaint of seizure. Cases were selected in which witnessed seizures had occurred in the field by family or EMS. Chart review included prehospital, nursing and physician records. Hypoglycemia was defined as blood glucose <60 mg/dL. Analysis included blood glucose, witnessed field seizure, initial mental status assessed by Glasgow Coma Scale (GCS), and further mental status assessments, along with age, sex, and medical history. Medical records were reviewed for subsequent BGT and patient outcome. A total 770 children were transported by EMS due to seizures. Four patients (0.5%) had recorded hypoglycemia in the field, yet only two received treatment to raise blood glucose. Additionally, one child (0.1%) was normoglycemic (81 mg/dL) in the field with hypoglycemia (43 mg/dL) in the ED but required no intervention. Two were found by EMS to have an ALOC (GCS ≤ 12) and hypoglycemia. Only the patient with hypoglycemia secondary to a suspected glipizide ingestion received ED glucose administration. The most common discharge diagnosis was simple febrile seizure (38.6%). Hypoglycemia in the pediatric seizure patient is extremely rare, thus universal field BGT has low utility and potential downstream effects. We propose a novel algorithm for the initial evaluation and

  13. The Causes and Consequences of Altered Glucose Metabolism in Cancer

    Science.gov (United States)

    2007-10-05

    result in scurvy when ascorbate is deficient from the diet . The iron and 2-oxoglutarate dependant dioxygenase family is known to contain several...to the disulfide, resulting in the reduction of FAD to FADH2 which is reoxidized by electron transfer to NAD+, to yield NADH and H+. B. Pyruvate

  14. Pulmonary biochemical alterations resulting from ozone exposure

    Energy Technology Data Exchange (ETDEWEB)

    Mustafa, M.G.; Lee, S.D.

    1976-07-01

    Metabolic response of lung tissue to ozone was studied in rats and monkeys after exposure of animals to various levels of ozone (0.1 to 0.8 ppM) for 1 to 30 days. In rats, 0.8 ppM ozone exposure resulted in a 40 to 50 percent augmentation of oxygen utilization in lung homogenate in the presence of an added substrate (e.g., succinate or 2-oxoglutarate). Activities of marker enzymes, viz. mitochondrial succinate-cytochrome c reductase; microsomal NADPH-cytochrome c reductase and cytosolic glucose-6-phosphate dehydrogenase, increased maximally (40 to 70 percent over control) after 3 to 4 days of exposure, and remained elevated throughout the 0.8 ppM ozone exposure for 30 days. In monkeys, the observations were the same except that the magnitude of biochemical changes was relatively smaller. Exposure of animals to lower levels of ozone resulted in proportionately smaller biochemical changes in the lung, and ozone effects were detectable up to the 0.2 ppM level. While 0.1 ppM ozone exposure was ineffective, dietary deficiency of vitamin E, a natural antioxidant, increased the sensitivity of rat lungs to this concentration of ozone. The results suggest that low-level ozone exposures may cause metabolic alterations in the lung, and that dietary supplementation of vitamin E may offer protection against oxidant stress.

  15. Cardiac expression of human type 2 iodothyronine deiodinase increases glucose metabolism and protects against doxorubicin-induced cardiac dysfunction in male mice.

    Science.gov (United States)

    Hong, Eun-Gyoung; Kim, Brian W; Jung, Dae Young; Kim, Jong Hun; Yu, Tim; Seixas Da Silva, Wagner; Friedline, Randall H; Bianco, Suzy D; Seslar, Stephen P; Wakimoto, Hiroko; Berul, Charles I; Russell, Kerry S; Lee, Ki Won; Larsen, P Reed; Bianco, Antonio C; Kim, Jason K

    2013-10-01

    Altered glucose metabolism in the heart is an important characteristic of cardiovascular and metabolic disease. Because thyroid hormones have major effects on peripheral metabolism, we examined the metabolic effects of heart-selective increase in T3 using transgenic mice expressing human type 2 iodothyronine deiodinase (D2) under the control of the α-myosin heavy chain promoter (MHC-D2). Hyperinsulinemic-euglycemic clamps showed normal whole-body glucose disposal but increased hepatic insulin action in MHC-D2 mice as compared to wild-type (WT) littermates. Insulin-stimulated glucose uptake in heart was not altered, but basal myocardial glucose metabolism was increased by more than two-fold in MHC-D2 mice. Myocardial lipid levels were also elevated in MHC-D2 mice, suggesting an overall up-regulation of cardiac metabolism in these mice. The effects of doxorubicin (DOX) treatment on cardiac function and structure were examined using M-mode echocardiography. DOX treatment caused a significant reduction in ventricular fractional shortening and resulted in more than 50% death in WT mice. In contrast, MHC-D2 mice showed increased survival rate after DOX treatment, and this was associated with a six-fold increase in myocardial glucose metabolism and improved cardiac function. Myocardial activity and expression of AMPK, GLUT1, and Akt were also elevated in MHC-D2 and WT mice following DOX treatment. Thus, our findings indicate an important role of thyroid hormone in cardiac metabolism and further suggest a protective role of glucose utilization in DOX-mediated cardiac dysfunction.

  16. Smectite alteration

    International Nuclear Information System (INIS)

    Anderson, D.M.

    1984-11-01

    This report contains the proceedings of a second workshop in Washington DC December 8-9, 1983 on the alteration of smectites intended for use as buffer materials in the long-term containment of nuclear wastes. It includes extended summaries of all presentations and a transcript of the detailed scientific discussion. The discussions centered on three main questions: What is the prerequisite for and what is the precise mechanism by which smectite clays may be altered to illite. What are likly sources of potassium with respect to the KBS project. Is it likely that the conversion of smectite to illite will be of importance in the 10 5 to the 10 6 year time frame. The workshop was convened to review considerations and conclusions in connection to these questions and also to broaden the discussion to consider the use of smectite clays as buffer materials for similar applications in different geographical and geological settings. SKBF/KBS technical report 83-03 contains the proceedings from the first workshop on these matters that was held at the State University of New York, Buffalo May 26-27, 1982. (Author)

  17. 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

  18. Glucose effectiveness in nondiabetic relatives

    DEFF Research Database (Denmark)

    Egede, M B; Henriksen, J-E; Durck, T T

    2014-01-01

    AIMS: Reduced glucose effectiveness is a predictor of future glucose tolerance in individuals with a family history of type 2 diabetes. We examined retrospectively at 10 years in normoglycemic relatives of diabetic subjects (RELs) the pathophysiological role of glucose effectiveness...... in the development of isolated impaired fasting glucose, glucose intolerance, and acute insulin release. METHODS: At 0 years, 19 RELs and 18 matched control subjects had glucose effectiveness (GE), insulin sensitivity, acute insulin release (AIR)IVGTT, and disposition index measured during an iv glucose tolerance...... test (IVGTT), using the minimal model analysis. At 0 and 10 years, oral glucose tolerance (OGTT) and AIROGTT were determined. RESULTS: At 0 years, fasting glucose (FG) and GE were raised in RELs, but insulin sensitivity and AIROGTT were reduced (P ≤ .05) compared with controls. At 10 years, RELs...

  19. Comparing glucose and insulin data from the two-hour oral glucose tolerance test in metabolic syndrome subjects and marathon runners.

    Science.gov (United States)

    Altuve, Miguel; Perpinan, Gilberto; Severeyn, Erika; Wong, Sara

    2016-08-01

    Glucose is the main energy source of the body's cells and is essential for normal metabolism. Two pancreatic hormones, insulin and glucagon, are involved in glucose home-ostasis. Alteration in the plasma glucose and insulin concentrations could lead to distinct symptoms and diseases, ranging from mental function impairment to coma and even death. Type 2 diabetes, insulin resistance and metabolic syndrome are typical examples of abnormal glucose metabolism that increase the risk for cardiovascular disease and mortality. The oral glucose tolerance test (OGTT) is a medical test used to screen for prediabetes, type 2 diabetes and insulin resistance. In the 5-sample 2-hour OGTT, plasma glucose and insulin concentrations are measured after a fast and then after oral intake of glucose, at intervals of 30 minutes. In this work, a statistical analysis is carried out to find significant differences between the five stages of the OGTT for plasma glucose and insulin data. In addition, the behavior of the glucose and insulin data is compared between subjects with the metabolic syndrome and marathon runners. Results show that marathon runners have plasma glucose and insulin levels significantly lower (p Insulin secretion decreases in marathon runners due to a significant reduction in plasma glucose concentration, but insulin secretion does not decrease in metabolic syndrome subjects due to insulin resistance, consequently plasma glucose concentration does not achieve normal levels.

  20. 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.

  1. NIR FRET Fluorophores for Use as an Implantable Glucose Biosensor

    Directory of Open Access Journals (Sweden)

    Majed DWEIK

    2008-12-01

    Full Text Available Development of an in vivo optical sensor requires the utilization of Near Infra Red (NIR fluorophores due to their ability to operate within the biological tissue window. Alexa Fluor 750 (AF750 and Alexa Fluor 680 (AF680 were examined as potential NIR fluorophores for an in vivo fluorescence resonance energy transfer (FRET glucose biosensor. AF680 and AF750 found to be a FRET pair and percent energy transfer was calculated. Next, the tested dye pair was utilized in a competitive binding assay in order to detect glucose. Concanavalin A (Con A and dextran have binding affinity, but in the presence of glucose, glucose displaces dextran due to its higher affinity to Con A than dextran. Finally, the percent signal transfer through porcine skin was examined. The results showed with approximately 4.0 mm porcine skin thickness, 1.98 % of the fluorescence was transmitted and captured by the detector.

  2. A study of glucose handling by Buddhist monks.

    Science.gov (United States)

    Aung, T; Myint, H; Thein, M

    1988-04-01

    Fourteen Buddhist monks and comparable male subjects were studied in relation to their handling of glucose after a meal (consisting of 1190 kcal, 29 g protein, 21 g fat and 221 g carbohydrate) and afterwards subjected to an oral glucose tolerance test (oGTT). The time course of blood glucose levels after the meal indicated that the monks had enhanced absorption and utilization of glucose. The monks were also found to have increased tolerance to glucose on oGTT. In addition the mean total serum cholesterol level in the monks (157.2 +/- 5.53 mg/dl) was found to be significantly higher than that of the control subjects (117.4 +/- 2.85 mg/dl).

  3. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... A A A Listen En Español Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical term for high ... function (data) { $('#survey-errors').remove(); $('.survey-form .form-group .survey-alert-wrap').remove(); if (data.submitSurveyResponse.success == ' ...

  4. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing ... Pinterest Youtube Instagram Diabetes Stops Here Blog Online Community Site ... Day Prediabetes My Health Advisor Tools to Know Your Risk Diabetes Basics ...

  5. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Monthly In Memory In Honor Become a Member En Español Type 1 Type 2 About Us Online ... Print Page Text Size: A A A Listen En Español Hyperglycemia (High Blood Glucose) Hyperglycemia is the ...

  6. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Diagnosing Diabetes and Learning About Prediabetes Type 2 Diabetes Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day Diabetes Basics ...

  7. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Research & Practice Ways to Give Close Are You at Risk? Home Prevention Diagnosing Diabetes and Learning About Prediabetes Type 2 Diabetes Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose ...

  8. All about Blood Glucose

    Science.gov (United States)

    ... may need a change in your meal plan,physical activity,or diabetes medicines.Keep track of when you’ve had ... glucose events.Note possible causes,such as unplanned physical activity.Then talk it over with your ... Diabetes Association    1–800–DIABETES (342–2383)    www. diabetes. ...

  9. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... around 4:00 a.m. to 5:00 a.m.). What are the Symptoms of Hyperglycemia? The signs and symptoms include the following: High blood glucose High levels of sugar in the urine Frequent urination Increased ...

  10. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... work with your doctor to find the safest way for you to lower your blood glucose level. Cutting down on the amount of food you eat might also help. Work with your dietitian to make changes in your meal plan. If exercise and changes ...

  11. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... You at Risk? Home Prevention Diagnosing Diabetes and Learning About Prediabetes Type 2 Diabetes Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day Diabetes Basics ...

  12. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... the safest way for you to lower your blood glucose level. Cutting down on the amount of food you eat might also help. Work with your dietitian to make changes in your meal plan. If exercise and changes in your diet ...

  13. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know ... We Support Your Doctor Clinical Practice Guidelines Patient Education Materials Scientific ... for School Projects How to Reference Our Site Diabetes Basics ...

  14. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... glucose) Dawn Phenomenon Checking for Ketones Tight Diabetes Control donate en -- A Future Without Diabetes - a-future- ... to the Association. Shopdiabetes.org: Your Stress-Free System for Family Dinners! - 2017-03-book-oclock-scramble. ...

  15. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... In Memory In Honor Become a Member En Español Type 1 Type 2 About Us Online Community ... Page Text Size: A A A Listen En Español Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical ...

  16. Muscle glucose metabolism following exercise in the rat

    DEFF Research Database (Denmark)

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

    1982-01-01

    both, the concentration of insulin that half-maximally stimulated glucose utilization (exercise, 150 muU/ml; control, 480 muU/ml) and modestly increased its maximum effect. The increase in insulin sensitivity persisted for 4 h following exercise, but was not present after 24 h. The rate-limiting step...... diminished synthase activity in situ. The possibility that exercise enhanced the ability of insulin to convert glycogen synthase D to an intermediate form of the enzyme, more sensitive to glucose-6-phosphate, remains to be explored. These results suggest that following exercise, glucose transport...

  17. Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes.

    Science.gov (United States)

    Satin, Leslie S; Butler, Peter C; Ha, Joon; Sherman, Arthur S

    2015-04-01

    Type 2 diabetes (T2DM) results when increases in beta cell function and/or mass cannot compensate for rising insulin resistance. Numerous studies have documented the longitudinal changes in metabolism that occur during the development of glucose intolerance and lead to T2DM. However, the role of changes in insulin secretion, both amount and temporal pattern, has been understudied. Most of the insulin secreted from pancreatic beta cells of the pancreas is released in a pulsatile pattern, which is disrupted in T2DM. Here we review the evidence that changes in beta cell pulsatility occur during the progression from glucose intolerance to T2DM in humans, and contribute significantly to the etiology of the disease. We review the evidence that insulin pulsatility improves the efficacy of secreted insulin on its targets, particularly hepatic glucose production, but also examine evidence that pulsatility alters or is altered by changes in peripheral glucose uptake. Finally, we summarize our current understanding of the biophysical mechanisms responsible for oscillatory insulin secretion. Understanding how insulin pulsatility contributes to normal glucose homeostasis and is altered in metabolic disease states may help improve the treatment of T2DM. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    H.G. Padilha

    2011-10-01

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

  19. Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes

    Science.gov (United States)

    Satin, Leslie S.; Butler, Peter C.; Ha, Joon; Sherman, Arthur S.

    2015-01-01

    Type 2 diabetes (T2DM) results when increases in beta cell function and/or mass cannot compensate for rising insulin resistance. Numerous studies have documented the longitudinal changes in metabolism that occur during the development of glucose intolerance and lead to T2DM. However, the role of changes in insulin secretion, both amount and temporal pattern has been understudied. Most of the insulin secreted from pancreatic beta cells of the pancreas is released in a pulsatile pattern, which is disrupted in T2DM. Here we review the evidence that changes in beta cell pulsatility occur during the progression from glucose intolerance to T2DM in humans, and contribute significantly to the etiology of the disease. We review the evidence that insulin pulsatility improves the efficacy of secreted insulin on its targets, particularly hepatic glucose production, but also examine evidence that pulsatility alters or is altered by changes in peripheral glucose uptake. Finally, we summarize our current understanding of the biophysical mechanisms responsible for oscillatory insulin secretion. Understanding how insulin pulsatility contributes to normal glucose homeostasis and is altered in metabolic disease states may help improve the treatment of T2DM. PMID:25637831

  20. Biodegradation and interaction of quinoline and glucose in dual substrates system.

    Science.gov (United States)

    Xu, Peng; Ma, Wencheng; Han, Hongjun; Hou, Baolin; Jia, Shengyong

    2015-03-01

    An indigenous mixed culture of microorganisms, isolated from a full-scale coal gasification wastewater treatment plant, was used in degrading quinoline in presence of glucose as an alternative carbon source. The results showed that biodegradation kinetics of both quinoline and glucose could be described by first-order reaction kinetics model. It was also found that the biodegradation rate of quinoline was accelerated by the presence of glucose, while glucose degradation was inhibited by the presence of quinoline. Both the biomass yield coefficient and specific growth rate were increased with the increasing of the glucose concentrations in the dual substrates system. A sum kinetics model was used to describe the relative effects of the two substrates on their individual uptakes. The interaction parameter values indicated that quinoline exhibits stronger inhibition on glucose degradation. But for glucose, its effect on quinoline utilization was stimulative. Furthermore, the stimulation was positively correlated with the concentration of glucose in the system.

  1. The Destiny of Glucose from a MicroRNA Perspective.

    Science.gov (United States)

    Mirra, Paola; Nigro, Cecilia; Prevenzano, Immacolata; Leone, Alessia; Raciti, Gregory Alexander; Formisano, Pietro; Beguinot, Francesco; Miele, Claudia

    2018-01-01

    Glucose serves as a primary, and for some tissues the unique, fuel source in order to generate and maintain the biological functions. Hyperglycemia is a hallmark of type 2 diabetes and is the direct consequence of perturbations in the glucose homeostasis. Insulin resistance, referred to as a reduced response of target tissues to the hormone, contributes to the development of hyperglycemia. The molecular mechanisms responsible for the altered glucose homeostasis are numerous and not completely understood. MicroRNAs (miRNAs) are now recognized as regulators of the lipid and glucose metabolism and are involved in the onset of metabolic diseases. Indeed, these small non-coding RNA molecules operate in the RNA silencing and posttranscriptional regulation of gene expression and may modulate the levels of kinases and enzymes in the glucose metabolism. Therefore, a better characterization of the function of miRNAs and a deeper understanding of their role in disease may represent a fundamental step toward innovative treatments addressing the causes, not only the symptoms, of hyperglycemia, using approaches aimed at restoring either miRNAs or their specific targets. In this review, we outline the current understanding regarding the impact of miRNAs in the glucose metabolism and highlight the need for further research focused on altered key kinases and enzymes in metabolic diseases.

  2. Greater variation in affect is associated with lower fasting plasma glucose

    Directory of Open Access Journals (Sweden)

    Sunjai Gupta

    2016-09-01

    Conclusion: This study has shown an inverse association between changes in affect and fasting plasma glucose. This unexpected finding suggests that the association between affect and glucose is more complex than previously thought. Fasting blood glucose may reflect the operation of homeostatic mechanisms that are disturbed in certain mental states and are associated, therefore, with altered risk of diabetes and related metabolic conditions. This may have implications for the management of those with such conditions and with mental disorders.

  3. Blood glucose in acute stroke

    DEFF Research Database (Denmark)

    Olsen, Tom Skyhøj

    2009-01-01

    Blood glucose is often elevated in acute stroke, and higher admission glucose levels are associated with larger lesions, greater mortality and poorer functional outcome. In patients treated with thrombolysis, hyperglycemia is associated with an increased risk of hemorrhagic transformation...... to the risk of inducing potentially harmful hypoglycemia has been raised. Still, basic and observational research is overwhelmingly in support of a causal relationship between blood glucose and stroke outcome and further research on glucose-lowering therapy in acute stroke is highly warranted....

  4. [Intelligent interpretation of home monitoring blood glucose data].

    Science.gov (United States)

    Dió, Mihály; Deutsch, Tibor; Biczók, Tímea; Mészáros, Judit

    2015-07-19

    Self monitoring of blood glucose is the cornerstone of diabetes management. However, the data obtained by self monitoring of blood glucose have rarely been used with the highest advantage. Few physicians routinely download data from memory-equipped glucose meters and analyse these data systematically at the time of patient visits. There is a need for improved methods for the display and analysis of blood glucose data along with a modular approach for identification of clinical problems. The authors present a systematic methodology for the analysis and interpretation of self monitoring blood glucose data in order to assist the management of patients with diabetes. This approach utilizes the followings 1) overall quality of glycemic control; 2) severity and timing of hypoglycemia and hyperglycemia; 3) variability of blood glucose readings; 4) various temporal patterns extracted from recorded data and 5) adequacy of self monitoring blood glucose data. Based on reliable measures of the quality of glycaemic control and glucose variability, a prioritized problem list is derived along with the probable causes of the detected problems. Finally, problems and their interpretation are used to guide clinicians to choose therapeutic actions and/or recommend behaviour change in order to solve the problems that have been identified.

  5. Effects of glucose ingestion on autonomic and cardiovascular measures during rest and mental challenge

    NARCIS (Netherlands)

    Synowski, S.J.; Kop, W.J.; Warwick, Z.S.; Waldstein, S.R.

    2013-01-01

    Background High levels of dietary sugar consumption may result in dysregulated glucose metabolism and lead to elevated cardiovascular disease risk via autonomic nervous system and cardiovascular dysfunction. Altered cardiovascular function can be examined using perturbation tasks such as mental

  6. The effect of DPP-4 inhibition with sitagliptin on incretin secretion and on fasting and postprandial glucose turnover in subjects with impaired fasting glucose

    DEFF Research Database (Denmark)

    Bock, Gerlies; Man, Chiara Dalla; Micheletto, Francesco

    2010-01-01

    Abstract Objective: Low Glucagon-like Peptide-1 (GLP-1) concentrations have been observed in impaired fasting glucose (IFG). It is uncertain if these abnormalities contribute directly to the pathogenesis of IFG and impaired glucose tolerance. Dipeptidyl peptidase-4 (DPP-4) inhibitors raise incretin...... period, the mixed meal was repeated. Results: As expected, subjects with IFG who received placebo did not experience any change in glucose concentrations. Despite raising intact GLP-1 concentrations, treatment with sitagliptin did not alter either fasting or postprandial glucose, insulin or C....... Conclusions: DPP-4 inhibition did not alter fasting or postprandial glucose turnover in people with IFG. Low incretin concentrations are unlikely to be involved in the pathogenesis of IFG....

  7. Fabrication of Functionalized Carbon Nanotube Buckypaper Electrodes for Application in Glucose Biosensors

    Directory of Open Access Journals (Sweden)

    Henry Papa

    2014-11-01

    Full Text Available A highly sensitive glucose detection method was developed using functionalized carbon nanotube buckypaper as a free standing electrode in an electrochemical biosensor. Glucose oxidase was immobilized onto various buckypaper samples in order to oxidize glucose resulting in a measureable current/voltage signal output of the biosensor. Cyclic voltammetry (CV and amperometry were utilized to determine the sensitivity of these buckypaper electrodes. Sensors of three different types of buckypaper were prepared and compared. These modified buckypaper electrode-based sensors showed much higher sensitivity to glucose compared to other electrochemical glucose sensors.

  8. Glucose metabolism and recycling by hepatocytes of OB/OB and ob/ob mice

    International Nuclear Information System (INIS)

    Lahtela, J.T.; Wals, P.A.; Katz, J.

    1990-01-01

    Hepatocytes were prepared from livers of ob/ob (obese diabetic) mice and their lean (OB/OB) siblings that had been fasted for 24 h. The hepatocytes were incubated with [U-14C, 2-3H]-, [U-14C, 3-3H]-, and [U-14C, 6-3H]glucose at concentrations from 20 to 120 mM. 14C was recovered mainly in CO2, glycogen, and lactate. Tritium was recovered in water and glycogen. The yield in labeled products from [2-3H]glucose ranged from two to three times that from [U-14C]glucose. The yields from [3-3H]- and [6-3H]glucose were similar, and 1.3-1.7 times that from [U-14C]glucose. At 40 mM, total utilization of glucose by obese mice was about twice that for lean mice, but there was little difference at 120 mM. The rate of recycling between glucose and glucose 6-phosphate was calculated. An equation to calculate the rate of recycling of glucose from the 2-3H/U-14C ratio in glycogen is derived in the APPENDIX. Our results show that (1) the utilization of glucose by hepatocytes from obese diabetic mice exceeds that of their lean controls, (2) the rate of glucose phosphorylation in both groups greatly exceeds glucose uptake and the rate of glycogen synthesis, (3) glucose phosphorylation represents a difference between a high glucokinase rate and hydrolysis of glucose 6-phosphate, and (4) recycling of glucose carbon between glucose 6-phosphate and pyruvate occurs within mouse hepatocytes

  9. Cellular distribution of glucose and monocarboxylate transporters in human brain white matter and multiple sclerosis lesions

    NARCIS (Netherlands)

    Nijland, P.G.; Michailidou, I.; Witte, M.E.; Mizee, M.R.; van der Pol, SM; Hof, B.; Reijerkerk, A.; Pellerin, L.; van der Valk, P.; de Vries, H.E.; van Horssen, J.

    2014-01-01

    To ensure efficient energy supply to the high demanding brain, nutrients are transported into brain cells via specific glucose (GLUT) and monocarboxylate transporters (MCT). Mitochondrial dysfunction and altered glucose metabolism are thought to play an important role in the progression of

  10. Prevalence of Sickle Cell Trait and Glucose 6 Phosphate ...

    African Journals Online (AJOL)

    Blood donation from sickle cell trait (SCT) and glucose-6-phosphate dehydrogenase (G6PD)-deficient donors might alter the quality of the donated blood during processing, storage or in the recipients' circulatory system. The aim of this study was to determine the prevalence of SCT and G6PD deficiency among blood ...

  11. 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

  12. Glucose and Aging

    Science.gov (United States)

    Ely, John T. A.

    2008-04-01

    When a human's enzymes attach glucose to proteins they do so at specific sites on a specific molecule for a specific purpose that also can include ascorbic acid (AA) at a high level such as 1 gram per hour during exposure. In an AA synthesizing animal the manifold increase of AA produced in response to illness is automatic. In contrast, the human non-enzymatic process adds glucose haphazardly to any number of sites along available peptide chains. As Cerami clarified decades ago, extensive crosslinking of proteins contributes to loss of elasticity in aging tissues. Ascorbic acid reduces the random non-enyzmatic glycation of proteins. Moreover, AA is a cofactor for hydroxylase enzymes that are necessary for the production and replacement of collagen and other structural proteins. We will discuss the relevance of ``aging is scurvy'' to the biochemistry of human aging.

  13. Programming of glucose-insulin homoeostasis

    DEFF Research Database (Denmark)

    Kongsted, Anna Hauntoft; Tygesen, M. P.; Husted, Sanne Vinter

    2014-01-01

    AIM: Exposure to adverse intra-uterine conditions can predispose for metabolic disorders later in life. By using a sheep model, we studied (i) how programming of glucose-insulin homoeostasis during late gestation is manifested later in life depending on the early post-natal dietary exposure and (ii......) whether dietary alteration in obese individuals can prevent adverse outcomes of early life programming. METHODS: During late gestation, twin-pregnant sheep were fed 100% (NORM) or 50% (LOW) of energy and protein requirements. After birth, offspring were exposed to a moderate (CONV) or high...

  14. Crosslinked basement membrane-based coatings enhance glucose sensor function and continuous glucose monitoring in vivo.

    Science.gov (United States)

    Klueh, Ulrike; Ludzinska, Izabela; Czajkowski, Caroline; Qiao, Yi; Kreutzer, Donald L

    2018-01-01

    Overcoming sensor-induced tissue reactions is an essential element of achieving successful continuous glucose monitoring (CGM) in the management of diabetes, particularly when used in closed loop technology. Recently, we demonstrated that basement membrane (BM)-based glucose sensor coatings significantly reduced tissue reactions at sites of device implantation. However, the biocompatible BM-based biohydrogel sensor coating rapidly degraded over a less than a 3-week period, which effectively eliminated the protective sensor coating. In an effort to increase the stability and effectiveness of the BM coating, we evaluated the impact of crosslinking BM utilizing glutaraldehyde as a crosslinking agent, designated as X-Cultrex. Sensor performance (nonrecalibrated) was evaluated for the impact of these X-Cultrex coatings in vitro and in vivo. Sensor performance was assessed over a 28-day time period in a murine CGM model and expressed as mean absolute relative difference (MARD) values. Tissue reactivity of Cultrex-coated, X-Cultrex-coated, and uncoated glucose sensors was evaluated over a 28-day time period in vivo using standard histological techniques. These studies demonstrated that X-Cultrex-based sensor coatings had no effect on glucose sensor function in vitro. In vivo, glucose sensor performance was significantly enhanced following X-Cultrex coating throughout the 28-day study. Histological evaluations of X-Cultrex-treated sensors demonstrated significantly less tissue reactivity when compared to uncoated sensors. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 7-16, 2018. © 2017 Wiley Periodicals, Inc.

  15. 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.

  16. Continued glucose output after re-feeding contributes to glucose intolerance in hyperthyroidism.

    OpenAIRE

    Holness, M J; Sugden, M C

    1987-01-01

    The effects of hyperthyroidism to elicit glucose intolerance after glucose administration were decreased under conditions where hepatic glucose output was suppressed. It is concluded that continued hepatic glucose output contributes to abnormal glucose tolerance in hyperthyroidism.

  17. Proposed Regulation of Gene Expression by Glucose in Rodent Heart

    Directory of Open Access Journals (Sweden)

    Martin E. Young

    2007-01-01

    Full Text Available Background: During pressure overload-induced hypertrophy, unloading-induced atrophy, and diabetes mellitus, the heart induces ‘fetal’ genes (e.g. myosin heavy chain β; mhcβ.Hypothesis: We propose that altered glucose homeostasis within the cardiomyocyte acts as a central mechanism for the regulation of gene expression in response to environmental stresses. The evidence is as follows. Methods and Results: Forced glucose uptake both ex vivo and in vivo results in mhc isoform switching. Restricting dietary glucose prevents mhc isoform switching in hearts of both GLUT1-Tg mice and rats subjected to pressure overload-induced hypertrophy. Thus, glucose availability correlates with mhc isoform switching under all conditions investigated. A potential mechanism by which glucose affects gene expression is through O-linked glycosylation of specific transcription factors. Glutamine:fructose-6-phosphate amidotransferase (GFAT catalyzes the flux generating step in UDP-N-acetylglucosamine biosynthesis, the rate determining metabolite in protein glycosylation. Ascending aortic constriction increased intracellular levels of UDP-N-acetylglucosamine, and the expression of gfat2, but not gfat1, in the rat heart.Conclusions: Collectively, the results strongly suggest glucose-regulated gene expression in the heart, and the involvement of glucose metabolites in isoform switching of sarcomeric proteins characteristic for the fetal gene program.

  18. Ambient but not local lactate underlies neuronal tolerance to prolonged glucose deprivation

    Science.gov (United States)

    Sobieski, Courtney; Shu, Hong-Jin

    2018-01-01

    Neurons require a nearly constant supply of ATP. Glucose is the predominant source of brain ATP, but the direct effects of prolonged glucose deprivation on neuronal viability and function remain unclear. In sparse rat hippocampal microcultures, neurons were surprisingly resilient to 16 h glucose removal in the absence of secondary excitotoxicity. Neuronal survival and synaptic transmission were unaffected by prolonged removal of exogenous glucose. Inhibition of lactate transport decreased microculture neuronal survival during concurrent glucose deprivation, suggesting that endogenously released lactate is important for tolerance to glucose deprivation. Tandem depolarization and glucose deprivation also reduced neuronal survival, and trace glucose concentrations afforded neuroprotection. Mass cultures, in contrast to microcultures, were insensitive to depolarizing glucose deprivation, a difference attributable to increased extracellular lactate levels. Removal of local astrocyte support did not reduce survival in response to glucose deprivation or alter evoked excitatory transmission, suggesting that on-demand, local lactate shuttling is not necessary for neuronal tolerance to prolonged glucose removal. Taken together, these data suggest that endogenously produced lactate available globally in the extracellular milieu sustains neurons in the absence of glucose. A better understanding of resilience mechanisms in reduced preparations could lead to therapeutic strategies aimed to bolster these mechanisms in vulnerable neuronal populations. PMID:29617444

  19. Regulation of glucose utilization and lipogenesis in adipose tissue ...

    Indian Academy of Sciences (India)

    ... in adipose tissue of control and diabetic animals of different ages are presented together with the effect of manganese on adipose tissue from high fat milk diet fed animals ... Hormone and Drug Research Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110 067, India; Molecular Medicine Unit, ...

  20. Regulation of Glucose Utilization by Estradiol in Breast Cancer

    Science.gov (United States)

    2014-10-01

    increase in glycolysis in addition to PFKFB3 siRNA studies. We are currently expanding our studies to include T47D (ER+) and MDA-MB231 (ER-) cells...We examined endogenous PFKFB3 protein expression in response to E2 in T47D cells and found that PFKFB3 protein significantly increased after 3h of...exposure to 10 nM E2 similarly to our MCF-7 studies (Figure 1). F2,6BP measurement in T47D cells is currently underway. Next, we determined the

  1. Glucose utilization and anti-oxidative mechanisms of the aqueous ...

    African Journals Online (AJOL)

    In South-west Nigeria, water decoctions of Hunteria umbellata seeds are highly valued by traditional healers in the local management of diabetes mellitus, obesity and hyperlipidemia. Previous studies hypothesized one of the antihyperglycemic mechanisms of the aqueous seed extract of Hunteria umbellata (HU) to be ...

  2. Multiple roles of glucose-6-phosphatases in pathophysiology: state of the art and future trends.

    Science.gov (United States)

    Marcolongo, Paola; Fulceri, Rosella; Gamberucci, Alessandra; Czegle, Ibolya; Banhegyi, Gabor; Benedetti, Angelo

    2013-03-01

    The endoplasmic reticulum enzyme glucose-6-phosphatase catalyzes the hydrolysis of glucose-6-phosphate to glucose and inorganic phosphate. The enzyme is a part of a multicomponent system that includes several integral membrane proteins; the catalytic subunit (G6PC) and transporters for glucose-6-phosphate, inorganic phosphate and glucose. The G6PC gene family presently includes three members, termed as G6PC, G6PC2, and G6PC3. Although the three isoforms show a moderate amino acid sequence homology, their membrane topology and catalytic site are very similar. The isoforms are expressed differently in various tissues. Mutations in all three genes have been reported to be associated with human diseases. The present review outlines the biochemical features of the G6PC gene family products, the regulation of their expression, their role in the human pathology and the possibilities for pharmacological interventions. G6PCs emerge as integrators of extra- and intracellular glucose homeostasis. Beside the well known key role in blood glucose homeostasis, the members of the G6PC family seem to play a role as sensors of intracellular glucose and of intraluminal glucose/glucose-6-phosphate in the endoplasmic reticulum. Since mutations in the three G6PC genes can be linked to human pathophysiological conditions, the better understanding of their functioning in connection with genetic alterations, altered expression and tissue distribution has an eminent importance.

  3. Quantitative estimation of the pathways followed in the conversion to glycogen of glucose administered to the fasted rat

    International Nuclear Information System (INIS)

    Scofield, R.F.; Kosugi, K.; Schumann, W.C.; Kumaran, K.; Landau, B.R.

    1985-01-01

    When [6- 3 H,6- 14 C]glucose was given in glucose loads to fasted rats, the average 3 H/ 14 C ratios in the glycogens deposited in their livers, relative to that in the glucoses administered, were 0.85 and 0.88. When [3- 3 H,3- 14 C]lactate was given in trace quantity along with unlabeled glucose loads, the average 3 H/ 14 C ratio in the glycogens deposited was 0.08. This indicates that a major fraction of the carbons of the glucose loads was converted to liver glycogen without first being converted to lactate. When [3- 3 H,6- 14 C]glucose was given in glucose loads, the 3 H/ 14 C ratios in the glycogens deposited averaged 0.44. This indicates that a significant amount of H bound to C-3, but not C-6, of glucose is removed within liver in the conversion of the carbons of the glucose to glycogen. This can occur in the pentose cycle and by cycling of glucose-6-P via triose phosphates. The contributions of these pathways were estimated by giving glucose loads labeled with [1- 14 C]glucose, [2- 14 C]glucose, [5- 14 C]glucose, and [6- 14 C]glucose and degrading the glucoses obtained by hydrolyzing the glycogens that deposited. Between 4 and 9% of the glucose utilized by the liver was utilized in the pentose cycle. While these are relatively small percentages a major portion of the difference between the ratios obtained with [3- 3 H]glucose and with [6- 3 H]glucose is attributable to metabolism in the pentose cycle

  4. Glucose-mediated control of ghrelin release from primary cultures of gastric mucosal cells

    Science.gov (United States)

    Sakata, Ichiro; Park, Won-Mee; Walker, Angela K.; Piper, Paul K.; Chuang, Jen-Chieh; Osborne-Lawrence, Sherri

    2012-01-01

    The peptide hormone ghrelin is released from a distinct group of gastrointestinal cells in response to caloric restriction, whereas its levels fall after eating. The mechanisms by which ghrelin secretion is regulated remain largely unknown. Here, we have used primary cultures of mouse gastric mucosal cells to investigate ghrelin secretion, with an emphasis on the role of glucose. Ghrelin secretion from these cells upon exposure to different d-glucose concentrations, the glucose antimetabolite 2-deoxy-d-glucose, and other potential secretagogues was assessed. The expression profile of proteins involved in glucose transport, metabolism, and utilization within highly enriched pools of mouse ghrelin cells and within cultured ghrelinoma cells was also determined. Ghrelin release negatively correlated with d-glucose concentration. Insulin blocked ghrelin release, but only in a low d-glucose environment. 2-Deoxy-d-glucose prevented the inhibitory effect of high d-glucose exposure on ghrelin release. mRNAs encoding several facilitative glucose transporters, hexokinases, the ATP-sensitive potassium channel subunit Kir6.2, and sulfonylurea type 1 receptor were expressed highly within ghrelin cells, although neither tolbutamide nor diazoxide exerted direct effects on ghrelin secretion. These findings suggest that direct exposure of ghrelin cells to low ambient d-glucose stimulates ghrelin release, whereas high d-glucose and glucose metabolism within ghrelin cells block ghrelin release. Also, low d-glucose sensitizes ghrelin cells to insulin. Various glucose transporters, channels, and enzymes that mediate glucose responsiveness in other cell types may contribute to the ghrelin cell machinery involved in regulating ghrelin secretion under these different glucose environments, although their exact roles in ghrelin release remain uncertain. PMID:22414807

  5. Microorganism Utilization for Synthetic Milk

    Science.gov (United States)

    Morford, Megan A.; Khodadad, Christina L.; Caro, Janicce I.; Spencer, LaShelle E.; Richards, Jeffery T.; Strayer, Richard F.; Birmele, Michele N.; Wheeler, Raymond M.

    2014-01-01

    A desired architecture for long duration spaceflight, like aboard the International Space Station or for future missions to Mars, is to provide a supply of fresh food crops for the astronauts. However, some crops can create a high proportion of inedible plant waste. The main goal of the Synthetic Biology project, Cow in a Column, was to produce the components of milk (sugar, lipid, protein) from inedible plant waste by utilizing microorganisms (fungi, yeast, bacteria). Of particular interest was utilizing the valuable polysaccharide, cellulose, found in plant waste, to naturally fuel-through microorganism cellular metabolism- the creation of sugar (glucose), lipid (milk fat), and protein (casein) in order to produce a synthetic edible food product. Environmental conditions such as pH, temperature, carbon source, aeration, and choice microorganisms were optimized in the laboratory and the desired end-products, sugars and lipids, were analyzed. Trichoderma reesei, a known cellulolytic fungus, was utilized to drive the production of glucose, with the intent that the produced glucose would serve as the carbon source for milk fat production and be a substitute for the milk sugar lactose. Lipid production would be carried out by Rhodosporidium toruloides, yeast known to accumulate those lipids that are typically found in milk fat. Results showed that glucose and total lipid content were below what was expected during this phase of experimentation. In addition, individual analysis of six fatty acids revealed that the percentage of each fatty acid was lower than naturally produced bovine milk. Overall, this research indicates that microorganisms could be utilized to breakdown inedible solid waste to produce useable products. For future work, the production of the casein protein for milk would require the development of a genetically modified organism, which was beyond the scope of the original project. Additional trials would be needed to further refine the required

  6. Estimating Utility

    DEFF Research Database (Denmark)

    Arndt, Channing; Simler, Kenneth R.

    2010-01-01

    A fundamental premise of absolute poverty lines is that they represent the same level of utility through time and space. Disturbingly, a series of recent studies in middle- and low-income economies show that even carefully derived poverty lines rarely satisfy this premise. This article proposes...... an information-theoretic approach to estimating cost-of-basic-needs (CBN) poverty lines that are utility consistent. Applications to date illustrate that utility-consistent poverty measurements derived from the proposed approach and those derived from current CBN best practices often differ substantially......, with the current approach tending to systematically overestimate (underestimate) poverty in urban (rural) zones....

  7. Random plasma glucose in serendipitous screening for glucose intolerance: screening for impaired glucose tolerance study 2.

    Science.gov (United States)

    Ziemer, David C; Kolm, Paul; Foster, Jovonne K; Weintraub, William S; Vaccarino, Viola; Rhee, Mary K; Varughese, Rincy M; Tsui, Circe W; Koch, David D; Twombly, Jennifer G; Narayan, K M Venkat; Phillips, Lawrence S

    2008-05-01

    With positive results from diabetes prevention studies, there is interest in convenient ways to incorporate screening for glucose intolerance into routine care and to limit the need for fasting diagnostic tests. The aim of this study is to determine whether random plasma glucose (RPG) could be used to screen for glucose intolerance. This is a cross-sectional study. The participants of this study include a voluntary sample of 990 adults not known to have diabetes. RPG was measured, and each subject had a 75-g oral glucose tolerance test several weeks later. Glucose intolerance targets included diabetes, impaired glucose tolerance (IGT), and impaired fasting glucose(110) (IFG(110); fasting glucose, 110-125 mg/dl, and 2 h glucose RPG to identify diabetes and 0.72 (0.68-0.75) to identify any glucose intolerance, both highly significant (p RPG values should be considered by health care providers to be an opportunistic initial screening test and used to prompt further evaluation of patients at risk of glucose intolerance. Such "serendipitous screening" could help to identify unrecognized diabetes and prediabetes.

  8. The Antiepileptic Ketogenic Diet Alters Hippocampal Transporter Levels and Reduces Adiposity in Aged Rats.

    Science.gov (United States)

    Hernandez, Abbi R; Hernandez, Caesar M; Campos, Keila T; Truckenbrod, Leah M; Sakarya, Yasemin; McQuail, Joseph A; Carter, Christy S; Bizon, Jennifer L; Maurer, Andrew P; Burke, Sara N

    2018-03-14

    Nutritional ketosis is induced by high fat/low carbohydrate dietary regimens, which produce high levels of circulating ketone bodies, shifting metabolism away from glucose utilization. While ketogenic diets (KD) were initially introduced to suppress seizures, they are garnering attention for their potential to treat a myriad of neurodegenerative and metabolic disorders that are associated with advanced age. The feasibility and physiological impact of implementing a long-term KD in old animals, however, has not been systematically examined. In this study, young and aged rats consumed a calorically- and nutritionally-matched KD or control diet for 12 weeks. All KD-fed rats maintained higher levels of BHB and lower levels of glucose relative to controls. However, it took the aged rats longer to reach asymptotic levels of BHB compared to young animals. Moreover, KD-fed rats had significantly less visceral white and brown adipose tissue than controls without a loss of lean mass. Interestingly, the KD led to significant alterations in protein levels of hippocampal transporters for monocarboxylates, glucose, and vesicular glutamate and gamma-aminobutyric acid. Most notably, the age-related decline in vesicular glutamate transporter expression was reversed by the KD. These data demonstrate the feasibility and potential benefits of KDs for treating age-associated neural dysfunction.

  9. Dietary glucose stimulus at larval stage modifies the carbohydrate metabolic pathway in gilthead seabream (Sparus aurata) juveniles: An in vivo approach using (14)C-starch.

    Science.gov (United States)

    Rocha, Filipa; Dias, Jorge; Geurden, Inge; Dinis, Maria Teresa; Panserat, Stephane; Engrola, Sofia

    2016-11-01

    The concept of nutritional programming was investigated in order to enhance the use of dietary carbohydrates in gilthead seabream juveniles. We assessed the long-term effects of high-glucose stimuli, exerted at the larval stage, on the growth performance, nutrient digestibility and metabolic utilization and gene expression of seabream juveniles, challenged with a high-carbohydrate intake. During early development, a group of larvae (control, CTRL) were kept under a rich-protein-lipid feeding regime whereas another group (GLU) was subjected to high-glucose stimuli, delivered intermittently over time. At juvenile stage, triplicate groups (IBW: 2.5g) from each fish nutritional background were fed a high-protein (59.4%) low-carbohydrate (2.0%) diet before being subjected to a low-protein (43.0%) high-carbohydrate (33.0%) dietary challenge for 36-days. Fish from both treatments increased by 8-fold their initial body weight, but neither growth rate, feed intake, feed and protein efficiency, nutrient retention (except lipids) nor whole-body composition were affected (P˃0.05) by fish early nutritional history. Nutrient digestibility was also similar among both groups. The metabolic fate of (14)C-starch and (14)C-amino acids tracers was estimated; GLU juveniles showed higher absorption of starch-derived glucose in the gut, suggesting an enhanced digestion of carbohydrates, while amino acid use was not affected. Moreover, glucose was less used for de novo synthesis of hepatic proteins and muscle glycogen from GLU fish (Pmetabolic data suggests that the early glucose stimuli may alter carbohydrate utilization in seabream juveniles. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Evaluation of long-term glucose homeostasis in lean and obese cats by use of continuous glucose monitoring.

    Science.gov (United States)

    Hoenig, Margarethe; Pach, Nicole; Thomaseth, Karl; Devries, Frerich; Ferguson, Duncan C

    2012-07-01

    To evaluate intraday and interday variations in glucose concentrations in cats and to test the utility of a continuous glucose monitoring system (CGMS). 6 lean and 8 long-term (> 5 years) obese cats. Blood glucose concentrations were measured during the course of 156 hours by use of a laboratory hexokinase-based reference method and a handheld glucometer. Interstitial glucose concentrations were evaluated with a CGMS. Paired measures of glucose concentrations obtained with the CGMS typically were marginally higher than concentrations for the reference method and less biased than concentrations obtained with the glucometer. This was partially confirmed by the concordance correlation coefficients of the concentration for the CGMS or glucometer versus the concentration for the reference method, although the correlation coefficients were not significantly different. Mean ± SD area under the curve for the glucose concentration (AUCG) did not differ significantly between lean (14.0 ± 0.5 g/dL•h) and obese (15.2 + 0.5 g/dL•h) cats during the 156-hour period, but one of the obese cats had a much higher AUCG. Within-day glucose variability was small in both lean and obese cats. Glucose homeostasis was maintained, even in long-term obese cats, and intraday glucose fluctuations were small. One obese cat might have been classified as prediabetic on the basis of the AUCG, which was approximately 25% higher than that of the other obese and lean cats. The CGMS can be useful in the evaluation of long-term effects of drugs or diet on glucose homeostasis in cats.

  11. Glucose Monitoring System Based on Osmotic Pressure Measurements

    Directory of Open Access Journals (Sweden)

    Alexandra LEAL

    2011-02-01

    Full Text Available This paper presents the design and development of a prototype sensor unit for implementation in a long-term glucose monitoring system suitable for estimating glucose levels in people suffering from diabetes mellitus. The system utilizes osmotic pressure as the sensing mechanism and consists of a sensor prototype that is integrated together with a pre-amplifier and data acquisition unit for both data recording and processing. The sensor prototype is based on an embedded silicon absolute pressure transducer and a semipermeable nanoporous membrane that is enclosed in the sensor housing. The glucose monitoring system facilitates the integration of a low power microcontroller that is combined with a wireless inductive powered communication link. Experimental verification have proven that the system is capable of tracking osmotic pressure changes using albumin as a model compound, and thereby show a proof of concept for novel long term tracking of blood glucose from remote sensor nodes.

  12. Impaired fasting glucose individuals: their response to oral glucose challenge

    International Nuclear Information System (INIS)

    Khan, M.N.A.; Dilawar, M.; Khan, F.A.; Sultana, S.

    2006-01-01

    To determine the frequency of Impaired Fasting Glucose (IFG) individuals in symptom free adults and their 2-h PG (two-hour plasma glucose) concentrations in standard Oral Glucose Tolerance Test (OGTT) with 75-g glucose. Fasting plasma glucose (FPG) of 859 symptom free adults was checked. Of them, 344(40%) were found to have IFG, who were subjected to standard OGTT with 75-g glucose and their 2-h PG results were recorded. Frequency distribution of FPG of 859 symptom free adults showed, 455(53%) were Normal Fasting Glucose (NFG 7.0 mmol/l). The difference in frequency of three groups of FPG was statistically significant (p<0.0001). Of 344 IFG individuals, who were subjected to standard OGTT, 182(53%) had Normal Glucose Tolerance (NGT), 127(37%) were Impaired Glucose Tolerance (IGT) and 35(10%) were diabetics. The difference in frequency of the three groups was statistically significant (p<0.0001). A significantly large number of asymptomatic adults are suffering from IFG in our set up. When IFG individuals are subjected to 75-g OGTT, their 2-h PG results showed about one third have IGT and also a significant number of IFG individuals are found to be patients of diabetes. (author)

  13. Glucose metabolism via the Entner-Doudoroff pathway in Campylobacter

    DEFF Research Database (Denmark)

    Vegge, Christina Skovgaard; van Rensburg, Melissa J. Jansen; Rasmussen, Janus Jagd

    2016-01-01

    enhanced stationary phase survival of a set of ED-positive C. coli isolates. Unexpectedly, glucose massively promoted floating biofilm formation in some of these ED-positive isolates. Metabolic profiling by gas chromatography-mass spectrometry revealed distinct responses to glucose in a low biofilm strain......), some glucose-utilizing isolates exhibit specific fitness advantages, including stationary-phase survival and biofilm production, highlighting key physiological benefits of this pathway in addition to energy conservation....

  14. Insulin induces an increase in cytosolic glucose levels in 3T3-L1 cells with inhibited glycogen synthase activation.

    Science.gov (United States)

    Chowdhury, Helena H; Kreft, Marko; Jensen, Jørgen; Zorec, Robert

    2014-10-02

    Glucose is an important source of energy for mammalian cells and enters the cytosol via glucose transporters. It has been thought for a long time that glucose entering the cytosol is swiftly phosphorylated in most cell types; hence the levels of free glucose are very low, beyond the detection level. However, the introduction of new fluorescence resonance energy transfer-based glucose nanosensors has made it possible to measure intracellular glucose more accurately. Here, we used the fluorescent indicator protein (FLIPglu-600µ) to monitor cytosolic glucose dynamics in mouse 3T3-L1 cells in which glucose utilization for glycogen synthesis was inhibited. The results show that cells exhibit a low resting cytosolic glucose concentration. However, in cells with inhibited glycogen synthase activation, insulin induced a robust increase in cytosolic free glucose. The insulin-induced increase in cytosolic glucose in these cells is due to an imbalance between the glucose transported into the cytosol and the use of glucose in the cytosol. In untreated cells with sensitive glycogen synthase activation, insulin stimulation did not result in a change in the cytosolic glucose level. This is the first report of dynamic measurements of cytosolic glucose levels in cells devoid of the glycogen synthesis pathway.

  15. Effects of glucose and insulin on fetal glucose oxidation and oxygen consumption

    International Nuclear Information System (INIS)

    Hay, W.W. Jr.; DiGiacomo, J.E.; Meznarich, H.K.; Hirst, K.; Zerbe, G.

    1989-01-01

    Glucose and insulin clamp experiments were performed in late-gestation fetal lambs to quantify the separate and combined effects of physiological concentrations of fetal glucose (G; 7.3-62.6 mg/dl) and insulin (I; 2-119 uU/ml) on fetal glucose metabolism and O2 consumption. Fetal glucose utilization rate (GUR) varied from 2.82 to 15.12 mg.min-1.kg-1. Fetal CO 2 production from fetal glucose carbon oxidation (CO 2 Pr) varied from 32 to 234 mumol.min-1.kg-1 and was directly related to G and I [CO 2 Pr = -0.00868 + 0.00578 (G) + 0.000901 (I) - 0.0000619 (G)2, r = 0.88] and to GUR (CO 2 Pr = 0.0159 GUR - 0.0130, r = 0.89). CO 2 Pr accounted for 54.7% of the mean GUR and for 35.9% of the mean umbilical O 2 uptake (UO2U), ranging from 26.0% in the control studies to 36.5% in hyperinsulinemic-euglycemic studies and to 45.1% in hyperinsulinemic-hyperglycemic studies. UO 2 U varied from 0.200 to I [UO 2 U = 0.303 + [0.000813 (G)] + [0.0000461 (I)], r = 0.89] and to GUR (UO2U = 0.0098 GUR + 0.275, r = 0.91). These results define independent (additive) effects of G and I on glucose oxidation in the late gestation fetal lamb and demonstrate the necessity for considering the levels of both G and I when studying these aspects of fetal metabolism

  16. 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

  17. CNC-bZIP protein Nrf1-dependent regulation of glucose-stimulated insulin secretion.

    Science.gov (United States)

    Zheng, Hongzhi; Fu, Jingqi; Xue, Peng; Zhao, Rui; Dong, Jian; Liu, Dianxin; Yamamoto, Masayuki; Tong, Qingchun; Teng, Weiping; Qu, Weidong; Zhang, Qiang; Andersen, Melvin E; Pi, Jingbo

    2015-04-01

    The inability of pancreatic β-cells to secrete sufficient insulin in response to glucose stimulation is a major contributing factor to the development of type 2 diabetes (T2D). We investigated both the in vitro and in vivo effects of deficiency of nuclear factor-erythroid 2-related factor 1 (Nrf1) in β-cells on β-cell function and glucose homeostasis. Silencing of Nrf1 in β-cells leads to a pre-T2D phenotype with disrupted glucose metabolism and impaired insulin secretion. Specifically, MIN6 β-cells with stable knockdown of Nrf1 (Nrf1-KD) and isolated islets from β-cell-specific Nrf1-knockout [Nrf1(b)-KO] mice displayed impaired glucose responsiveness, including elevated basal insulin release and decreased glucose-stimulated insulin secretion (GSIS). Nrf1(b)-KO mice exhibited severe fasting hyperinsulinemia, reduced GSIS, and glucose intolerance. Silencing of Nrf1 in MIN6 cells resulted in oxidative stress and altered glucose metabolism, with increases in both glucose uptake and aerobic glycolysis, which is associated with the elevated basal insulin release and reduced glucose responsiveness. The elevated glycolysis and reduced glucose responsiveness due to Nrf1 silencing likely result from altered expression of glucose metabolic enzymes, with induction of high-affinity hexokinase 1 and suppression of low-affinity glucokinase. Our study demonstrated a novel role of Nrf1 in regulating glucose metabolism and insulin secretion in β-cells and characterized Nrf1 as a key transcription factor that regulates the coupling of glycolysis and mitochondrial metabolism and GSIS. Nrf1 plays critical roles in regulating glucose metabolism, mitochondrial function, and insulin secretion, suggesting that Nrf1 may be a novel target to improve the function of insulin-secreting β-cells.

  18. Effects of glucose infusion on hepatic and muscle glycogenolysis in exercising dogs.

    Science.gov (United States)

    Issekutz, B

    1981-05-01

    Hepatic glucose production (Ra) and the rate of utilization of nonglucose sources (essentially muscle glycogen) were measured in dogs running on a treadmill (15%, 133 m/min) with indwelling catheters in the jugular vein and carotid artery. A mixture of [3-3H]glucose and [U-14C]glucose was used as tracer according to the principles of the primed constant-rate infusion techniques. Glucose was infused intravenously at a rate (12 mg.kg-1.min-1) about 20% higher than the endogenous glucose Ra in exercising dogs. Glucose infusion started either at the beginning of the run or midexercise. Plasma insulin (IRI), glucagon (IRG), and cAMP levels were measured. Exogenous glucose prevented the usual decline of both plasma glucose and IRI without causing hyperglycemia. Exercise increased the molar ratio of IRG/IRI from 0.7 to 1.4, and glucose infusion lowered it to the resting value. The rise of plasma cAMP was slowed significantly. Both the hepatic glucose Ra and intramuscular glycogenolysis were strongly inhibited and the metabolic clearance rate of glucose was increased by 60-100%. The ratio of the specific activities of [14C]lactate to [14C]glucose indicated that 75-95% of the lactate turnover arose from plasma glucose. The corresponding value in the control group was 40-50%. It is concluded that in prolonged exercise the decline of both plasma glucose and insulin play a major role in preserving glucose homeostasis, by limiting the glucose uptake of the working muscle and by helping to achieve an approximately equal contribution of the liver and the muscle glycogen for the elevated glycolysis.

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

    Science.gov (United States)

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

    2013-08-01

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

  20. 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

  1. 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.

  2. High glucose-mediated oxidative stress impairs cell migration.

    Directory of Open Access Journals (Sweden)

    Marcelo L Lamers

    Full Text Available Deficient wound healing in diabetic patients is very frequent, but the cellular and molecular causes are poorly defined. In this study, we evaluate the hypothesis that high glucose concentrations inhibit cell migration. Using CHO.K1 cells, NIH-3T3 fibroblasts, mouse embryonic fibroblasts and primary skin fibroblasts from control and diabetic rats cultured in 5 mM D-glucose (low glucose, LG, 25 mM D-glucose (high glucose, HG or 25 mM L-glucose medium (osmotic control--OC, we analyzed the migration speed, protrusion stability, cell polarity, adhesion maturation and the activity of the small Rho GTPase Rac1. We also analyzed the effects of reactive oxygen species by incubating cells with the antioxidant N-Acetyl-Cysteine (NAC. We observed that HG conditions inhibited cell migration when compared to LG or OC. This inhibition resulted from impaired cell polarity, protrusion destabilization and inhibition of adhesion maturation. Conversely, Rac1 activity, which promotes protrusion and blocks adhesion maturation, was increased in HG conditions, thus providing a mechanistic basis for the HG phenotype. Most of the HG effects were partially or completely rescued by treatment with NAC. These findings demonstrate that HG impairs cell migration due to an increase in oxidative stress that causes polarity loss, deficient adhesion and protrusion. These alterations arise, in large part, from increased Rac1 activity and may contribute to the poor wound healing observed in diabetic patients.

  3. Glucose Regulates the Expression of the Apolipoprotein A5 Gene

    Energy Technology Data Exchange (ETDEWEB)

    Fruchart, Jamila; Nowak, Maxime; Helleboid-Chapman, Audrey; Jakel, Heidelinde; Moitrot, Emmanuelle; Rommens, Corinne; Pennacchio, Len A.; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2008-04-07

    The apolipoprotein A5 gene (APOA5) is a key player in determining triglyceride concentrations in humans and mice. Since diabetes is often associated with hypertriglyceridemia, this study explores whether APOA5 gene expression is regulated by alteration in glucose homeostasis and the related pathways. D-glucose activates APOA5 gene expression in a time- and dose-dependent manner in hepatocytes, and the glycolytic pathway involved was determined using D-glucose analogs and metabolites. Together, transient transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation assays show that this regulation occurs at the transcriptional level through an increase of USF1/2 binding to an E-box in the APOA5 promoter. We show that this phenomenon is not due to an increase of mRNA or protein expression levels of USF. Using protein phosphatases 1 and 2A inhibitor, we demonstrate that D-glucose regulates APOA5 gene via a dephosphorylation mechanism, thereby resulting in an enhanced USF1/2-promoter binding. Last, subsequent suppressions of USF1/2 and phosphatases mRNA through siRNA gene silencing abolished the regulation. We demonstrate that APOA5 gene is up regulated by D-glucose and USF through phosphatase activation. These findings may provide a new cross talk between glucose and lipid metabolism.

  4. SPCE based glucose sensor employing novel thermostable glucose dehydrogenase, FADGDH: blood glucose measurement with 150nL sample in one second.

    Science.gov (United States)

    Yamaoka, Hideaki; Sode, Koji

    2007-01-01

    Self-monitoring of blood glucose (SMBG) is an important component of the modern therapy for diabetes mellitus. Thanks to the current progress in electronics and sensor fabrication technology, both the time and the blood sample volume required for the measur