Glucose neurotoxicity

Neurons have a constantly high glucose demand, and unlike muscle cells they cannot accommodate episodic glucose uptake under the influence of insulin. Neuronal glucose uptake depends on the extracellular concentration of glucose, and cellular damage can ensue after persistent episodes of hyperglycaemia--a phenomenon referred to as glucose neurotoxicity. This article reviews the pathophysiological manifestation of raised glucose in neurons and how this can explain the major components of diabetic neuropathy.     

烷基胺玻璃固定化葡萄糖氧化酶测定血糖

定量分析血糖在门诊和许多疾病如糖尿病,甲状腺机能抗进,粘液腺癌．垂体机能减退。肾上腺机能减退和妨碍葡萄糖吸收等疾病的诊断有重要意义。测定葡萄糖有很多方法,采用葡萄糖氧化酶比色法,由于操作简便．专一性强,灵敏度高,因此比较适合用于常规测定⑴。但是葡萄糖氧化酶的价格高。把酶固定在不溶于水的支持物上,酶可以重复使用,因此可以降低成本。虽然葡萄糖氧化酶固定在烷基胺玻璃上。在连续流动系统中测定葡萄糖,但烷基胺固定的酶还没有用来测定血糖。一般来说．烷基胺玻璃抗微生物的腐蚀。有很广的pH适应性和不同溶剂如乙醇和丙酮的稳定性。本文报道利用烷基胺玻璃珠固定葡萄糖氧化酶常规分析血糖。     

Contribution of Glucose Phosphorylation to Glucose Metabolism in Brevibacterium fuscum

When the ‘dihydroxyacetone-fermentation’ was carried out in a steady state by the cells of Br. fuscum, it was suggested that the consumption rate of glucose in the medium might be regulated at the initial stages of glucose degradation such as; (a) glucose isomerization, (b) glucose dehydrogenation, and (c) glucose phosphorylation. Of these three enzymatic reactions, the isomerization and the dehydrogenation were proved to be unable to occur or negligible in vivo. So, in consideration of the pool sizes of Mg^{+ +}, Pi, H⁺, glucose, G6P*, ATP, ADP, etc., the intracellular glucokinase** activity was calculated. Results indicate that glucokinase reaction may be the limiting factor for direct glucose metabolism in Br. fuscum.     

Mathematical Modeling of Renal Tubular Glucose Absorption after Glucose Load

A partial differential Progressive Tubular Reabsorption (PTR) model, describing renal tubular glucose reabsorption and urinary glucose excretion following a glucose load perturbation, is proposed and fitted to experimental data from five subjects. For each subject the Glomerular Filtration Rate was estimated and both blood and urine glucose were sampled following an Intra-Venous glucose bolus. The PTR model was compared with a model representing the conventional Renal Threshold Hypothesis (RTH). A delay bladder compartment was introduced in both formulations. For the RTH model, the average threshold for glycosuria varied between 9.90±4.50 mmol/L and 10.63±3.64 mmol/L (mean ± Standard Deviation) under different hypotheses; the corresponding average maximal transport rates varied between 0.48±0.45 mmol/min (86.29±81.22 mg/min) and 0.50±0.42 mmol/min (90.62±76.15 mg/min). For the PTR Model, the average maximal transports rates varied between 0.61±0.52 mmol/min (109.57±93.77 mg/min) and 0.83±0.95 mmol/min (150.13±171.85 mg/min). The time spent by glucose inside the tubules before entering the bladder compartment varied between 1.66±0.73 min and 2.45±1.01 min.The PTR model proved much better than RTH at fitting observations, by correctly reproducing the delay of variations of glycosuria with respect to the driving glycemia, and by predicting non-zero urinary glucose elimination at low glycemias. This model is useful when studying both transients and steady-state glucose elimination as well as in assessing drug-related changes in renal glucose excretion.     

Growth and Glucose Repression Are Controlled by Glucose Transport in Saccharomyces cerevisiae Cells Containing Only One Glucose Transporter

A set of Saccharomyces cerevisiae strains with variable expression of only the high-affinity Hxt7 glucose transporter was constructed by partial deletion of the HXT7 promoter in vitro and integration of the gene at various copy numbers into the genome of an hxt1-7 gal2 deletion strain. The glucose transport capacity increased in strains with higher levels of HXT7 expression. The consequences for various physiological properties of varying the glucose transport capacity were examined. The control coefficient of glucose transport with respect to growth rate was 0.54. At high extracellular glucose concentrations, both invertase activity and the rate of oxidative glucose metabolism increased manyfold with decreasing glucose transport capacity, which is indicative of release from glucose repression. These results suggest that the intracellular glucose concentration produces the signal for glucose repression.     

Relations between Blood Glucose and Hepatic Glucose Production in Newborn Dogs

No correlation was found between the concentration of glucose in blood plasma and the rate of hepatic glucose production in newborn pups aged 2½-112 hours. During the first few hours of life the hypoglycaemic response to insulin was small or absent. Later the response seemed exaggerated mainly owing to a slow recovery to normoglycaemia. This latter observation can be entirely accounted for by the lack of a feedback mechanism between the plasma concentration and the hepatic rate of production of glucose.     

Calorimetric Glucose Determination by Glucose Oxidase —Methylene Blue

The reaction between glucose and methylene blue, catalyzed by glucose oxidase (GOD)was analysed calorimetrically. The amount of heat produced under saturating methylene blue concentrations ( > 10^?2 mol/1)was measured with glucose concentration and time as parameters (kinetic procedure) Kinetic constants (pseudo one substrate kinetics) were derived from the experimental data: K_M(glucose)= 1.18 × 10^?3 mol/l and V_max = 0.085 J/mg GOD min (3.89 · 10^?6 mol/mg GOD min) Comparison of caloric with optical measurements gave an enthalpy of reaction of 22.52 kJ/mol. Considering the observed substrate inhibition, glucose determinations are possible up to glucose concentrations of 0.1 mol/l.     

Regulation of Endogenous Glucose Production in Glucose Transporter 4 Over-Expressing Mice

Strategies to amplify whole-body glucose disposal are key therapies to treat type 2 diabetes. Mice that over-express glucose transporter 4 (Glut4) in skeletal muscle, heart, and adipose tissue (G4Tg) exhibit increased fasting glucose disposal and thus lowered blood glucose. Intriguingly, G4Tg mice also exhibit improved insulin-stimulated suppression of endogenous glucose production even though Glut4 is not present in the liver. It is unclear, however, if hepatic gluco-regulation is altered in G4Tg mice in the basal, non-insulin-stimulated state. The current studies were performed to examine fasting hepatic glucose metabolism in G4Tg mice and to determine whether gluco-regulatory adaptations exist in the non-insulin-stimulated condition. To test this question, phloridzin-glucose clamps were used to match blood glucose and pancreatic hormone levels while tracer dilution techniques were used to measure glucose flux. These techniques were performed in chronically-catheterized, conscious, and un-stressed 5h-fasted G4Tg and wild-type (WT) littermates. Results show reduced blood glucose, hepatic glycogen content, and hepatic glucokinase (GK) activity/expression as well as higher endogenous glucose production, glucose disposal, arterial glucagon, and hepatic glucose-6-phosphatase (G6Pase) activity/expression in G4Tg mice versus WT controls. Clamping blood glucose for 90 min at ∼115 mg/dLin G4Tg and WT mice normalized nearly all variables. Notably, however, net hepatic glycogen synthetic rates were disproportionately elevated compared to changes in blood glucose. In conclusion, these studies demonstrate that basal improvements in glucose tolerance due to increased uptake in extra-hepatic sites provoke important gluco-regulatory adaptations in the liver. Although changes in blood glucose underlie the majority of these adaptations, net hepatic glycogen synthesis is sensitized. These data emphasize that anti-diabetic therapies that target skeletal muscle, heart, and/or adipose tissue likely positively impact the liver.     

Glucose Availability to Individual Cerebral Structures Is Correlated to Glucose Metabolism

Regional cerebral glucose influx was measured using quantitative autoradiography after the intravenous infusion of [2-¹⁴C]glucose for a period of 10 or 20 s. Glucose influx varied considerably among structures over an almost threefold range. When compared with rates of regional glucose utilization, a significant correlation by region was found between glucose influx and utilization, demonstrating that the glucose supply to individual cere bral structures is closely matched to their metabolic needs.     

Glucose Polyester Biosynthesis. Purification and Characterization of a Glucose Acyltransferase

Glandular trichomes of the wild tomato species Lycopersicon pennellii secrete 2,3,4-O-tri-acyl-glucose (-Glc), which contributes to insect resistance. A Glc acyltransferase catalyzes the formation of diacyl-Glc by disproportionating two equivalents of 1-O-acyl-beta-Glc, a high-energy molecule formed by a UDP-Glc dependent reaction. The acyltransferase was purified 4,900-fold from L. pennellii leaves by polyethylene glycol fractionation, diethylaminoethyl chromatography, concanavalin A affinity chromatography, and chromatofocusing. The acyltransferase possesses an isoelectric point of 4.8, a relative molecular mass around 110 kD, and is composed of 34- and 24-kD polypeptides as a heterotetramer. The 34- and 24-kD proteins were partially sequenced. The purified enzyme catalyzes both the disproportionation of 1-O-acyl-beta-Glcs to generate 1,2-di-O-acyl-beta-Glc and anomeric acyl exchange between 1-O-acyl-beta-Glc and Glc.     

Glycolysis Controls Plasma Membrane Glucose Sensors To Promote Glucose Signaling in Yeasts

Sensing of extracellular glucose is necessary for cells to adapt to glucose variation in their environment. In the respiratory yeast Kluyveromyces lactis, extracellular glucose controls the expression of major glucose permease gene RAG1 through a cascade similar to the Saccharomyces cerevisiae Snf3/Rgt2/Rgt1 glucose signaling pathway. This regulation depends also on intracellular glucose metabolism since we previously showed that glucose induction of the RAG1 gene is abolished in glycolytic mutants. Here we show that glycolysis regulates RAG1 expression through the K. lactis Rgt1 (KlRgt1) glucose signaling pathway by targeting the localization and probably the stability of Rag4, the single Snf3/Rgt2-type glucose sensor of K. lactis. Additionally, the control exerted by glycolysis on glucose signaling seems to be conserved in S. cerevisiae. This retrocontrol might prevent yeasts from unnecessary glucose transport and intracellular glucose accumulation.     

Glucose transport and apoptosis

The transport and metabolism of glucose modify programmed cell death in a number of different cell types. This review presents three cell death paradigms that link a decrease in glucose transport to apoptosis. Although these pathways overlap, the glucose-dependent stimuli that trigger cell death differ. These paradigms include glucose deprivation-induced ATP depletion and stimulation of the mitochondrial death pathway cascade; glucose deprivation-induced oxidative stress and triggering of Bax-associated events including the JNK/MAPK signalling pathways; and finally hypoglycemia-regulated expression of HIF-1, stabilization of p53 leading to an increase in p53-associated apoptosis. Several examples of each paradigm are presented. Future studies of glucose transport-associated apoptotic events will allow better understanding of the role of cellular metabolism in programmed cell death.