Combined effect of 2-deoxy-D-glucose and exercise on plasma catecholamine response.

2-Deoxy-D-glucose (2-DG) is a nonmetabolizable analogue of glucose that, by competitive inhibition of glucose utilization, produces a central neuroglucopenia and a peripheral hyperglycemia. This glucopenic agent was used to gain more insight into the combined effects of central glucopenia and exercise on plasma catecholamine response. This was carried out by comparing one group of exercising (26 m/min, 0% grade) rats injected with 2-DG (2-DG-EX; 250 mg/kg iv) with two control groups: one group of exercising rats injected with a saline solution (SAL-EX) and one group of resting rats injected with 2-DG (2-DG-RE). Significant (P less than 0.05) increases in blood glucose levels were observed 10 min after administration of 2-DG (7.2-13.8 and 7.3-12.4 mmol/l in 2-DG-EX and 2-DG-RE groups, respectively). These elevated blood glucose levels were maintained throughout the experiment in the 2-DG-RE condition but decreased in 2-DG-EX rats to levels observed in the SAL-EX group after 45 min of running (13.8-8.0 mmol/l). The combination of 2-DG-induced neuroglucopenia and exercise resulted in an additive response of norepinephrine (0.59 vs. 0.34 and 0.34 ng/ml; t = 12 min) and an amplified epinephrine response (1.4 vs. 0.37 and 0.31 ng/ml; t = 12 min) compared with the responses to each stimulus alone (2-DG-EX vs. 2-DG-RE and SAL-EX, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Elevation of plasma triglyceride levels due to 2-deoxy-D-glucose in conscious rats

Hypertriglyceridemia due to 2-deoxy-D-glucose administration was observed in conscious rats. Plasma triglyceride levels were elevated dose-dependently 2 or 3 hrs after administration of 2-deoxy-D-glucose (5-40 mg/100 g body weight). Prior to the rises in triglyceride, plasma epinephrine levels were elevated rapidly, whereas plasma insulin was not increased depspite continuous hyperglycemia. Elevation of plasma triglyceride was suppressed by addition of phentolamine, whereby insulin release was remarkably enhanced. Plasma lipoprotein lipase release by heparin infusion was significantly suppressed 2 hr after 2-deoxy-D-glucose administration. In conclusion, it is suggested that the hypertriglyceridemic effect of 2-deoxy-D-glucose may be mediated by decreased clearance of endogeneous lipoprotein particles (mostly chylomicrons) attributable to a lowered lipoprotein lipase activity.     

Threshold levels of generalist predation determine consumer response to resource pulses

Many ecological systems are characterized by brief periods of increased resource availability called resource pulses. Empirical studies suggest that some populations of primary consumers grow rapidly in response to resource pulses, but others instead remain at low abundance despite increases in resource availability. Previous theory suggests that the lack of increase in primary consumers might be due to predators, which can respond to increased prey density both numerically, by increasing their own population, and functionally, by killing prey at a faster rate. The complexity of potential population responses to resource pulses can be assessed with simulations, but analytical conditions determining when one observes qualitatively distinct dynamics have yet to be identified. Here we use a graphical method based on a bifurcation diagram to derive the conditions leading to qualitatively distinct steady state and transient prey population dynamics as levels of predation (abundance and diversity) vary. When predation thresholds are crossed, consumer populations respond numerically to increases in their resources and provide a secondary resource pulse to their predators and parasites. These community dynamics have broad implications for the impact of changing predator communities on insect and rodent population outbreaks, which are economically and epidemiologically important.     

Regulation of circulating levels of the crustacean hyperglycemic hormone: evidence for a dual feedback control system

The effects of glutamate, aspartate, glycine, proline, alanine, taurine, glycerol, glucose and lactate injections on the haemolymph levels of the crustancean hyperglycemic hormone and/or glucose and lactate in the shore crab, Carcinus maenas, were investigated. Only glucose and lactate caused significant changes of hyperglycaemic hormone levels. Glucose injections resulted in a drop of both hormone and lactate, while lactate had an opposite effect, i.e. it raised both crustacean hormone and glucose levels. The results suggest that during increases in glycolytic flux, lactate may cause a release of hormone by a positive feedback mechanism. The hormone would then stimulate glycogenolysis, thus increasing glucose availability. If more glucose is released than is metabolized, excess glucose may leak from the cells and suppress crustancean hyperglycemic hormone release from the X-organ/sinus gland complex by negative feedback.Abbreviations ABTS 2,2-azino-bis (3-ethylbenzthiazoline sulphonic acid) - ANOVA one-way analysis of variance - BSA bovine serum albumin - BW body weight - CHH crustacean hyperglycemic hormone - ELISA cnzyme-liked immunosorbent assay - GIH gonadinhibiting hormone - IgG immunoglobin G - MIH moult-inhibiting hormone - MTGXO medulla terminalis X-organ - PB sodium phosphate buffer - PBS phosphate buffered saline - Pi inorganic phosphate - XO-SG X-organ-sinus gland complex     

In vivo effect of 2-deoxy-D-glucose on adenine nucleotide levels in the liver and skeletal muscle of rats

The present report indicates that 2-deoxy-D-glucose (2-DG) at a single dose causing reduction of Tre has no influence on liver and skeletal muscle content of ATP, ADP and AMP, the ATP/ADP ratio, energy charge potential (ECP) and total adenine nucleotides (TAN). After administration of 2-DG for 3) successive days, the level of ATP, ATP/ADP ratio, the values of ECP and TAN are decreased both in the liver and skeletal muscle. However, 72 hours after the last injection of 2-DG adenine nucleotide contents returned to the values observed in control group, indicating that the in vivo effect of this glucose analogue is fully reversible.     

Decomposition reactions of amino sugars: the dehydration of 2-amino-2-deoxy-D-glucose

The stability of the title compound (1) was investigated at 100° in acidified aqueous solutions containing, in some instances, glycine or pyridine. In strong acid (3M hydrochloric acid), the sugar was relatively stable, and no identifiable decomposition-products were observed. In less-acidic solutions (≤0.5M hydrochloric acid) in the presence of glycine, substantial decomposition occurred with the production of 5-(hydroxymethyl)-2-furaldehyde (2) in 0.5-5.2% yield. The major dehydration products, however (up to 18% of the starting sugar), were pyrazine derivatives bearing dissimilar, four-carbon, acyclic-sugar side-chains attached to C-2 and C-5 of the ring, respectively, arising, most probably, from C-3-C-6 of the original sugar molecules. When the conversions were performed in deuterium oxide solution, carbon-bound isotope was observed in 2 (at the aldehyde carbon and at C-3) and, in the pyrazine derivatives, on the ring (positions 3 and 6), and on the sugar-derived, side-chains.     

Automation of a fluorometric method for the determination of 2-deoxy-D-glucose

A continuous-flow fluorometric procedure for the determination of 2-deoxy-D-glucose (2DG) is described. The method utilizes Technicon Autoanalyzer equipment and modules, and is based on the acid-catalyzed condensation of 3,5-diaminobenzoic acid with 2DG. The procedure permits analysis of 20 samples/h, is sensitive to concentrations of 2DG as low as 0.2 mg/100 ml, and requires sample volumes of only 0.25 ml. 2DG can be quantitatively measured in serum samples or tissue extracts without requiring deproteinization. Glucose does not interfere with the assay while 2-deoxy-D-ribose develops a fluorescence which is about 15% of that produced by the same amount of 2DG and is additive when both deoxy sugars are present together. The procedure is accurate, reproducible, and fast, and can be run continuously.     

Naloxone inhibits the plasma epinephrine response to ACTH but not to 2-deoxy-D-glucose in rats

Intravenous injection of (1-24) ACTH and 2-deoxy-d-glucose (2DG) stimulated the plasma epinephrine and norepinephrine levels in pentobarbital-anesthetized male rats. Naloxone, a specific opiate antagonist, inhibited the plasma epinephrine response to ACTH but not to 2DG. Norepinephrine release induced by ACTH or 2DG was not affected by naloxone. These results suggest that the opioid peptidergic synapse might be involved in the ACTH- but not in the 2DG-induced epinephrine release.     

Drawing the future: Stomatal response to CO2 levels

Gas exchange between the plant and the atmosphere is regulated by controlling both the stomatal density and the aperture of the stomatal pore. Environmental factors such as light, the level of atmospheric CO₂ and hormones regulate stomatal development and/or function. Because atmospheric CO₂ levels have been rising since the Industrial Revolution, and it is predicted that they will continue doing so in the future, an understanding of the CO₂ signalling mechanisms in the stomatal responses will help to know how plants were in the past and will allow predicting how they will respond to climate change in the near future. This article covers the recent knowledge of the CO₂ signalling mechanisms that regulate both stomatal function and development.Key words: Arabidopsis, CO₂, development, epidermis, gas exchange, leaf, patterning, stoma     

Eimeria apsheronica in the goat: endogenous development and host cellular response

Most first generation schizonts of Eimeria apsheronica developed in the jejunum; others were distributed throughout the small intestine and occasionally in the caecum. Some were also found in the mesenteric lymph nodes, which were oedematous and haemorrhagic. In the intestine, haemorrhage and congestion were seen before parasites were detected, and continued throughout all later stages. Schizonts occurred in the lamina propria and occasionally in the submucosa, where they sometimes caused a cellular inflammatory response. Schizonts were first seen at 8 days post-infection (DPI); they had poorly defined nuclei and were enclosed in a capsule-like wall. At 16 DPI, many had matured, had a mean size of 125 x 82 microns, and were filled with numerous spindle-shaped merozoites, which were in ranks and loops. At 18 and 20 DPI, when small white lesions (1-3 mm in diameter) were observed in the jejunum and elsewhere in the small intestine, a second generation of schizonts, macrogametes, microgametocytes and maturing oocysts were seen, in the epithelial cells of the small intestine and caecum. Their mean sizes, respectively, were: 26.2 x 18.9, 24.7 x 18.5, 30.2 x 21.7 and 26.6 x 19.3 microns. Macrogametes contained basophilic central and eosinophilic peripheral granules. The sexual stages were associated with a generalized cellular inflammatory response.     

High-affinity transport and phosphorylation of 2-deoxy-D-glucose in synaptosomes

2-Deoxy-d -glucose (2 DG) entered synaptosomes (from rat brain) by a high-affinity, Na⁺-independent glucose transport system with a K_m, of 0.24 mM. 3-O-methyl-glucose, D-glucose, and phloretin were competitive inhibitors of 2-DG transport with K_i's of 7 mM, 64 μM, and 0·75 μM, respectively. Insulin was without effect. 2-DG uptake was also saturable at high substrate concentrations with an apparent low affinity K_m, of 75 mM, where the K_l, for glucose was 17.5 mM. We are not certain whether the rate-limiting step for the low-affinity uptake system is attributable to transport or phosphorylation. However, the high-affinity glucose transport system probably is a special property of neuronal cell membranes and could be useful in helping to distinguish separated neurons from glial cells.     

Transport and metabolism of 2-deoxy-D-glucose by Rhodotorula glutinis

2-Deoxy-D-glucose transport by Rhodotorula glutinis is an active process. The intracellular concentration of free deoxyglucose after 15 min incubation of Rhodotorula cells with this sugar was 230 times the extracellular concentration. Although cell extracts at this time contained more 2-deoxy-D-glucose 6-phosphate than deoxyglucose, pulse-labelling experiments demonstrated that deoxyglucose is transported as the free sugar and subsequently phosphorylated. After transport, Rhodotorula cells metabolize deoxyglucose. The major metabolites during 30-90 min incubations were determined to be 2-deoxy-D-glucose 6-phosphate, 2-deoxy-D-glucitol, 2-deoxy-D-gluconate and 2,2'-dideoxy-alpha, alpha'-trehalose. Rhodotorula glutinis also degrades deoxyglucose to CO2. The concentrations of intermediates in this pathway were too low to detect and resolve in extracts of control cells. In 2,4-dinitrophenol-poisoned cells, however, it appears that deoxyglucose degradation is restricted largely to loss of C-1 as CO2 and it was possible to identify 1-deoxy-D-ribulose 5-phosphate as an intermediate presumably arising from metabolism of deoxyglucose by the oxidative portion of the hexose monophosphate pathway.     

Differential membrane redistribution of P2X receptor isoforms in response to osmotic and hyperglycemic stress in the rat lens

P2X_{1, 2, 3, 4, 6 and 7} are all expressed in a differentiation-dependent manner in the rat lens. However, in the lens outer cortex the subcellular distribution of all P2X isoforms is predominantly associated with a pool of receptors located in cytoplasmic vesicles. Here we investigate whether osmotic and hyperglycemic stress can alter the subcellular distribution of this cytoplasmic pool of P2X receptors. We show that in a discrete zone of the deeper outer cortex an isoform and stimulus-specific shift in the subcellular distribution of P2X receptors occurs from the cytoplasm to defined membrane domains. In response to hypertonic stress P2X₁ and P2X₄ isoforms became more closely associated with the broad sides of fiber cells, while under hypotonic conditions P2X₄ and P2X₆ isoforms associate with the narrow side membranes. No such changes in subcellular distribution were observed for P2X_{2,3 and 7} isoforms. Lens cultured in 50 mM glucose exhibited cell swelling in this zone but only P2X₄ associated with narrow side membranes. Our results indicate P2X receptors can be differentially recruited to specific membrane domains of lens fiber cells by osmotic and hyperglycemic stress. Furthermore they suggest the involvement of specific P2X isoforms in the regulation of fiber cell volume and the initiation of diabetic cataract.