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Low Glucose (low + glucose)
Terms modified by Low Glucose Selected AbstractsDifferential effects of low glucose concentrations on seizures and epileptiform activity in vivo and in vitroEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2006Anne Kirchner Abstract In vivo, severe hypoglycemia is frequently associated with seizures. The hippocampus is a structure prone to develop seizures and seizure-induced damage. Patients with repeated hypoglycemic episodes have frequent memory problems, suggesting impaired hippocampal function. Here we studied the effects of moderate hypoglycemia on primarily generalized flurothyl-induced seizures in vivo and, using EEG recordings, we determined involvement of the hippocampus in hypoglycemic seizures. Moderate systemic hypoglycemia had proconvulsant effects on flurothyl-induced clonic (forebrain) seizures. During hypoglycemic seizures, seizure discharges were recorded in the hippocampus. Thus, we continued the studies in combined entorhinal cortex,hippocampus slices in vitro. However, in vitro, decreases in extracellular glucose from baseline 10 mm to 2 or 1 mm did not induce any epileptiform discharges. In fact, low glucose (2 and 1 mm) attenuated preexisting low-Mg2+ -induced epileptiform activity in the entorhinal cortex and hippocampal CA1 region. Osmolarity compensation in low-glucose solution using mannitol impaired slice recovery. Additionally, using paired-pulse stimuli we determined that there was no impairment of GABAA inhibition in the dentate gyrus during glucopenia. The data strongly indicate that, although forebrain susceptibility to seizures is increased during moderate in vivo hypoglycemia and the hippocampus is involved during hypoglycemic seizures, glucose depletion in vitro contributes to an arrest of epileptiform activity in the system of the entorhinal cortex,hippocampus network and there is no impairment of net GABAA inhibition during glucopenia. [source] Neurotransmitter and neuromodulatory mechanisms at peripheral arterial chemoreceptorsEXPERIMENTAL PHYSIOLOGY, Issue 6 2010Colin A. Nurse The control of breathing depends critically on sensory inputs to the central pattern generator of the brainstem, arising from peripheral arterial chemoreceptors located principally in the carotid bodies (CBs). The CB receptors, i.e. glomus or type I cells, are excited by chemical stimuli in arterial blood, particularly hypoxia, hypercapnia, acidosis and low glucose, which initiate corrective reflex cardiorespiratory and cardiovascular adjustments. Type I cells occur in clusters and are innervated by petrosal afferent fibres. Synaptic specializations (both chemical and electrical) occur between type I cells and petrosal terminals, and between neighbouring type I cells. This, together with the presence of a wide array of neurotransmitters and neuromodulators linked to both ionotropic and metabotropic receptors, allows for a complex modulation of CB sensory output. Studies in several laboratories over the last ,20 years have provided much insight into the transduction mechanisms. More recent studies, aided by the development of a co-culture model of the rat CB, have shed light on the role of neurotransmitters and neuromodulators in shaping the afferent response. This review highlights some of these developments, which have contributed to our current understanding of information processing at CB chemoreceptors. [source] Cell resilience in species life spans: a link to inflammation?AGING CELL, Issue 4 2010Caleb E. Finch Summary Species differences in life span have been attributed to cellular survival during various stressors, designated here as ,cell resilience'. In primary fibroblast cultures, cell resilience during exposure to free radicals, hypoglycemia, hyperthermia, and various toxins has shown generally consistent correlations with the species characteristic life spans of birds and mammals. However, the mechanistic links of cell resilience in fibroblast cultures to different species life spans are poorly understood. We propose that certain experimental stressors are relevant to somatic damage in vivo during inflammatory responses of innate immunity, particularly, resistance to reactive oxygen species (ROS), low glucose, and hyperthermia. According to this hypothesis, somatic cell resilience determines species differences in longevity during repeated infections and traumatic injuries in the natural environment. Infections and injury expose local fibroblasts and other cells to ROS generated by macrophages and to local temperature elevations. Systemically, acute phase immune reactions cause hypoglycemia and hyperthermia. We propose that cell resilience to somatic stressors incurred in inflammation is important in the evolution of longevity and that longer-lived species are specifically more resistant to immune-related stressors. This hypothesis further specifies Kirkwood's disposable soma theory. We suggest expanding the battery of stressors and markers used for comparative studies to additional cell types and additional parameters relevant to host defense and to their ecological specificities. [source] Homeostasis of neuroactive amino acids in cultured cerebellar and neocortical neurons is influenced by environmental cuesJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1-2 2005Helle Waagepetersen Abstract Neuronal function is highly influenced by the extracellular environment. To study the effect of the milieu on neurons from cerebellum and neocortex, cells from these brain areas were cultured under different conditions. Two sets of cultures, one neocortical and one cerebellar neurons, were maintained in media containing [U- 13C]glucose for 8 days at initial concentrations of 12 and 28 mM glucose, respectively. Other sets of cultures (8 days in vitro) maintained in a medium containing initially 12 mM glucose were incubated subsequently for 4 hr either by addition of [U- 13C]glucose to the culture medium (final concentration 3 mM) or by changing to fresh medium containing [U- 13C]glucose (3 mM) but without glutamine and fetal calf serum. 13C Nuclear magnetic resonance (NMR) spectra revealed extensive ,-aminobutyric acid (GABA) synthesis in both cultured neocortical and cerebellar neurons after maintenance in medium containing [U- 13C]glucose for 8 days, whereas no aspartate labeling was observed in these spectra. Mass spectrometry analysis, however, revealed high labeling intensity of aspartate, which was equal in the two types of neurons. Addition of [U- 13C]glucose (4 hr) on Day 8 in culture led to a similar extent of labeling of GABA in neocortical and in cerebellar cultures, but the cellular content of GABA was considerably higher in the neocortical neurons. The cellular content of alanine was similar regardless of culture type. Comparing the amount of labeling, however, cerebellar neurons exhibited a higher capacity for alanine synthesis. This is compatible with the fact that cerebellar neurons could ameliorate a low alanine content after culturing in low glucose (12 mM) by a 4-hr incubation in medium containing 3 mM glucose. A low glucose concentration during the culture period and a subsequent medium change were associated with decreases in glutathione and taurine contents. Moreover, glutamate and GABA contents were reduced in cerebellar cultures under either of these conditions. In neocortical neurons, the GABA content was decreased by simultaneous exposure to low glucose and change of medium. These conditions also led to an increase in the aspartate content in both types of cultures, although most pronounced in the neocortical neurons. Further experiments are needed to elucidate these phenomena that underline the impact of extracellular environment on amino acid homeostasis. © 2004 Wiley-Liss, Inc. [source] Antioxidant Protection Mechanisms And Arachidonic Acid Synthesis Are Altered In Schwann Cells Grown In Elevated GlucoseJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2000C Miinea Accumulating evidence points to oxidative stress as an important factor in the onset of diabetic neuropathy. We have investigated the status of antioxidant protection mechanisms in immortalized rat Schwann cells cultured in high (30 and 50 mM) concentrations of glucose. As compared to growth in 5 mM glucose, the cells contained 40% less reduced glutathione (n =8, p < 0.01). Total superoxide dismutase activity was diminished by more than 50% (n=3; p < 0.001), whereas catalase activity was unchanged. The cellular NADH/NAD+ ratio was progressively increased with increasing medium glucose concentrations. Our previous findings have established that upon exposure of cultured cells to elevated glucose, the proportions of arachidonic acid-containing molecular species (ACMS) in phospholipids are decreased in a pattern similar to alterations exhibited by diabetic nerve. To examine whether biosynthesis of arachidonic acid might be perturbed, confluent cells maintained in either high or low glucose were incubated with either [14C]linoleic acid (18:2) or [14C]dihomo-,-linolenic acid (20:3) and radioactivity incorporated into molecular species of major phospholipid classes was measured. The incorporation of 18:2 either as unchanged fatty acid or into ACMS did not differ as a function of glucose concentration. Negligible labeled 18:3 or 20:3 molecular species were detected. In contrast, the uptake of 20:3 into 18:1/20:4 and 16:0/20:4 phosphatidylcholine and 18:1/20:4 phosphatidylethanolamine, but not into 20:3-containing molecular species, was significantly reduced in cells cultured in 30 mM glucose. These data imply that ,5 desaturase activity is decreased in cells exposed to elevated glucose. This reduced enzyme activity could adversely affect polyunsaturated fatty acid metabolism and might arise as a consequence of impaired scavenging of reactive oxygen species. (Supported by NIH grant DK30577) [source] Low-dose prostacyclin in treatment of severe brain trauma evaluated with microdialysis and jugular bulb oxygen measurementsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2000P.-O. Grände Background: The endogenous substance prostacyclin is a substance with the potential to improve microcirculation and oxygenation around contusions in the brain following a head trauma by its vasodilatory, antiaggregatory and antiadhesive effects. Microdialysis measurements of local concentrations of selected interstitial substances in the brain, and measurements of venous jugular bulb oxygenation reflecting overall brain oxygenation, might be useful to evaluate possible therapeutic effects of a specific therapy, such as treatment with prostacyclin. Methods: This case report study on six patients, of whom five were given prostacyclin, includes cerebral microdialysis measurements of interstitial lactate (n=5), pyruvate (n=3), glycerol (n=5) and glucose (n=4), and is combined with measurements of venous jugular bulb oxygenation in three of the patients. One microdialysis catheter was placed adjacent to a contusion, and in four of the patients another catheter was also placed in the contralateral less injured side for comparison. Low-dose prostacyclin infusion (0.5,1.0 ng kg,1 min,1) was started when lactate concentrations in the more injured side was raised at a constant level for more than 10 h. The study also includes one patient used as control to whom no prostacyclin was given. Results: Lactate was markedly lower in the less injured than in the more injured area of the brain. During the prostacyclin infusion elevated lactate and lactate/pyruvate ratio were reduced. Elevated glycerol decreased, a low glucose increased and jugular bulb blood oxygenation increased following start of prostacyclin. The control patient showed an increase in lactate and lactate/pyruvate ratio. Conclusion: The microdialysis data combined with the jugular bulb oxygenation data indicated that low-dose prostacyclin exerts effects compatible with improved oxygenation and reduced cell damage in the severely traumatised brain. [source] Loss of TIP1;1 aquaporin in Arabidopsis leads to cell and plant deathTHE PLANT JOURNAL, Issue 6 2004Shisong Ma Summary Arabidopsis TIP1;1 (,TIP) is a member of the tonoplast family of aquaporins (AQP). Using RNA interference (RNAi) we reduced TIP1;1 to different extent in various lines. When most severely affected, miniature plants died, a phenotype partially complemented by the TIP1;1 homolog McMIP-F. Less severely affected lines produced small plants, early senescence, and showed lesion formation. The relative water content in TIP1;1 RNAi plants was not significantly affected. Global expression profiling suggested a disturbance in carbon metabolism in RNAi lines with upregulated transcripts for functions in carbon acquisition and respiration, vesicle transport, signaling and transcription, and radical oxygen stress. Metabolite profiles showed low glucose, fructose, inositol, and threonic, succinic, fumaric, and malic acids, but sucrose levels were similar to WT. Increased amounts were found for raffinose and several unknown compounds. TIP1;1 RNAi plants also contained high starch and apoplastic carbohydrate increased. A GFP-TIP1;1 fusion protein indicated tonoplast location in spongy mesophyll cells, and high signal intensity in palisade mesophyll associated with vesicles near plastids. Signals in vascular tissues were strongest not only in vesicle-like structures but also outlined large vacuoles. Compromised routing of carbohydrate and lack of sucrose provision for cell-autonomous functions seems to characterize this RNAi phenotype. We suggest a function for TIP1;1 in vesicle-based metabolite routing through or between pre-vacuolar compartments and the central vacuole. Phenotype and expression characteristics support a view of TIP1;1 functioning as a marker for vesicles that are targeted to the central vacuole. [source] Metabolism of PER.C6TM cells cultivated under fed-batch conditions at low glucose and glutamine levelsBIOTECHNOLOGY & BIOENGINEERING, Issue 1 2006Luis Maranga Abstract This is the first study to examine PER.C6TM cell glucose/energy and glutamine metabolism with fed-batch cultures at controlled low glutamine, low glucose, and simultaneous low glucose and low glutamine levels. PER.C6TM cell metabolism was investigated in serum-free suspension bioreactors at two-liter scale. Control of glucose and/or glutamine concentrations had a significant effect on cellular metabolism leading to an increased efficiency of nutrient utilization, altered byproduct synthesis, while having no effect on cell growth rate. Cultivating cells at a controlled glutamine concentration of 0.25 mM reduced qGln and q by approximately 30%, qAla 85%, and qNEAA 50%. The fed-batch control of glutamine also reduced the overall accumulation of ammonium ion by approximately 50% by minimizing the spontaneous chemical degradation of glutamine. No major impact upon glucose/energy metabolism was observed. Cultivating cells at a glucose concentration of 0.5 mM reduced qGlc about 50% and eliminated lactate accumulation. Cells exhibited a fully oxidative metabolism with Y of approximately 6 mol/mol. However, despite no increase in qGln, an increased ammonium ion accumulation and Y were also observed. Effective control of lactate and ammonium ion accumulation by PER.C6TM cells was achieved using fed-batch with simultaneously controlled glucose and glutamine. A fully oxidative glucose metabolism and a complete elimination of lactate production were obtained. The qGln value was again reduced and, despite an increased q compared with batch culture, ammonium ion levels were typically lower than corresponding ones in batch cultures, and the accumulation of non-essential amino acids (NEAA) was reduced about 50%. In conclusion, this study shows that PER.C6TM cell metabolism can be confined to a state with improved efficiencies of nutrient utilization by cultivating cells in fed-batch at millimolar controlled levels of glucose and glutamine. In addition, PER.C6TM cells fall into a minority category of mammalian cell lines for which glutamine plays a minor role in energy metabolism. © 2006 Wiley Periodicals, Inc. [source] 2125: High glucose sensitizes human retinal endothelial cells for IFN-g-mediated apoptosisACTA OPHTHALMOLOGICA, Issue 2010R NAGARAJ Purpose The biochemical mechanisms by which inflammatory cytokines cause damage in the diabetic retina are poorly understood. Indoelamine 2, 3-dioxygenase (IDO) is an inducible by IFN-, enzyme and is the first enzyme of the kynurenine pathway, which produces cytotoxic kynurenines. In this study we have investigated the role of IDO in apoptosis of human retinal capillary endothelial cells (HREC) under hyperglycemic conditions. Methods HREC were cultured in medium containing high glucose (25 mM) or low glucose (7.5 mM) and incubated with 1-100 U/ml of IFN-,. IDO activity was measured by an HPLC assay. Expression of IFN-, receptor 1, and activation of the JAK-STAT signaling pathway along with activation of PKC-, was assessed by Western blotting. HREC apoptosis was measured by Hoechst staining. The role of IDO in HREC apoptosis was evaluated in the presence specific chemical inhibitors of the kynurenine pathway. Results IFN-, dose-dependently activated JAK-STAT signaling and PKC-,, and upregulated IDO. The IDO-mediated tryptophan oxidation led to formation of kynurenines, which was followed by chemical modification of proteins by kynurenines in HREC. These changes were accompanied by production of reactive oxygen species (ROS) and depletion of protein-free thiols. IFN-, inhibited cell cycle at low concentrations and caused caspase-3-mediated apoptosis and at higher concentrations, and those effects were amplified in the presence of high glucose in HREC. We found that IFN-, mediated cytotoxicity in HREC was primarily due to ROS generated by 3-hydroxykynurenine. Conclusion Our results suggest that high glucose sensitizes HREC to deleterious effects IFN-, and provide a novel mechanistic pathway for retinal capillary endothelial cell death in diabetes. [source] | |||||||||||||