Viral effects on metabolism: changes in glucose and glutamine utilization during human cytomegalovirus infection

Human cytomegalovirus (HCMV) infection causes dramatic alterations of intermediary metabolism, similar to those found in tumor cells. In infected cells, glucose carbon is not completely broken down by the tricarboxylic acid (TCA) cycle for energy; instead, it is used biosynthetically. This process requires increased glucose uptake, increased glycolysis and the diversion of glucose carbon, in the form of citrate, from the TCA cycle for use in HCMV-induced fatty acid biosynthesis. The diversion of citrate from the TCA cycle (cataplerosis) requires induction of enzymes to promote glutaminolysis, the conversion of glutamine to α-ketoglutarate to maintain the TCA cycle (anaplerosis) and ATP production. Such changes could result in heretofore uncharacterized pathogenesis, potentially implicating HCMV as a subtle cofactor in many maladies, including oncogenesis. Recognition of the effects of HCMV, and other viruses, on host cell metabolism will provide new understanding of viral pathogenesis and novel avenues for antiviral therapy.     

Corticosteroid-incuded changes in glucose metabolism of chondrocytes

Summary Immature mice were treated for up to 12 weeks with daily doses of triamcinolone diacetate. Using quantitative histochemical methods, the proximal epiphyseal plate of the humerus was studied at regular intervals. By the tenth injection significant decrease was noted in the acid glycosaminoglycans content (25%) and in the neutral mucopolysaccharides (30%). Concomitantly, a marked increase was noted in the intracellular depots of glycogen (70%). It is suggested that the hormone's antiglycolytic effect in cartilage caused the glucose metabolic pathway to divert in the direction of glycogen synthesis, and thereby interfered with the normal synthetic pathway of the chondrocytes. The hormone's primary effect on the cells' hexose metabolism could be responsible, at least in part, for its inhibitory influence on bone growth.Supported in part by Technion Research Grant No. 180-069Presented in part at the Fifth International Congress of Histochemistry and Cytochemistry held in Bucharest, 1976     

Hexose metabolism in pancreatic islets: preferential utilization of mitochondrial ATP for glucose phosphorylation

The respective contribution of exogenous and intramitochondrially formed ATP to D-glucose phosphorylation by mitochondria-bound hexokinase was examined in both rat liver and pancreatic islet mitochondria by comparing the generation of D-glucose 6-[32P]phosphate from exogenous [gamma-32P]ATP to the total rate of D-[U-14C]glucose phosphorylation. In liver mitochondria, the fractional contribution of exogenous ATP to D-glucose phosphorylation ranged from 4 to 74%, depending on the availability of endogenous ATP formed by either oxidative phosphorylation or in the reaction catalyzed by adenylate kinase. Likewise, in islet mitochondria exposed to exogenous ATP but deprived of exogenous nutrient, about 60% of D-glucose phosphorylation was supported by mitochondrial ATP. Such a fractional contribution was further increased in the presence of ADP and succinate, and suppressed by mitochondrial poisons. It is concluded that, in islet like in liver mitochondria, mitochondrial ATP is used preferentially to exogenous ATP as a substrate for D-glucose phosphorylation by mitochondria-bound hexokinase. This may favour the maintenance of a high cytosolic ATP concentration in glucose-stimulated islet cells.     

Effect of cadmium intoxication on glucose utilization in energy metabolism of muscles

The influence of cadmium intoxication on carbohydrate metabolism in skeletal muscles and liver of the male Wistar rats has been studied. Cadmium was administered as cadmium acetate in a dose of 0.3 mg Cd2+/kg body weight for three months. At the same time the control rats were injected with 0.9% NaCl. The animals were decapitated and samples of their skeletal muscles: the soleus muscle (composed mainly of red slow twitch fibers; ST) the gastrocnemius muscle containing two types of fibers (white fast twitch fibers FTb and red fast twitch fibers, FTa) and the liver were dissected out. In the samples of muscles, liver and serum contents of glycogen, glucose, pyruvate and lactate, as well as activities of hexokinase, pyruvate kinase and lactate dehydrogenase were measured. Intoxication of rats with cadmium for three months resulted in a reduction of glycolytic enzymes in the serum, ST and FTa muscle fibers and in the liver but did not change the activities of glycolytic enzymes in the FTb muscle fibers. The data obtained for the concentrations of glycogen in the liver and skeletal muscles suggest different mechanisms of cadmium influence on glycogen utilization in these organs.     

Impact of seasonal changes in stream metabolism on nitrate concentrations in an urban stream

Nitrate (NO₃ ^?) dynamics in urban streams differ from many natural streams due to stormwater runoff, sewage inputs, decreased groundwater discharge, often limited hyporheic exchange, increased primary productivity, and limited carbon input. We investigated NO₃ ^? dynamics in a first-order urban stream in Syracuse, NY, which has urbanized headwaters and a geomorphologically natural downstream section. Twice-monthly water sampling, NO₃ ^? injection tests, NO₃ ^? isotopic analysis, filamentous algae mat density, and riparian shading were used to identify processes regulating NO₃ ^? dynamics in the stream over a 12-month period. The urban headwater reach had low NO₃ ^? (0.006–0.2 mg N/L) in the spring through fall, with a minimum uptake length of 900 m, no canopy cover, and high algae mat density. The downstream natural reach (100% canopy cover during the summer and low algae mat density) had nitrate concentrations between 0.6 and 1.2 mg N/L from winter to summer, which decreased during autumn leaf-off. In the urban reach, autotrophic uptake by filamentous green algae is a major NO₃ ^? sink in summer. In the natural reach, the addition of organic matter to the stream at leaf-off led to a decrease in NO₃ ^? concentration followed by an increase in NO₃ ^? concentration in winter as gross primary productivity decreased. This study shows that the balance between autotrophy and heterotrophy in urban streams is variable and depends on an interplay of drivers such as temperature, light, and carbon inputs that are mediated by the riparian ecosystem.     

Bioavailability of starch and postprandial changes in splanchnic glucose metabolism in pigs

Changes in splanchnic metabolism in pigs were assessed after meals containing slowly or rapidly digested starch. The pigs were fed a mixed meal containing a "slow" native (n = 5) or a "rapid" pregelatinized (n = 5) cornstarch naturally enriched with [(13)C]glucose. Absorption of [(13)C]glucose was monitored by the arteriovenous difference technique, and infusion of D-[6, 6-(2)H(2)]glucose in the jugular vein was used to calculate the systemic appearance of [(13)C]glucose. Arteriovenous balance data obtained during a 12-h study period showed that the fraction of ingested glucose equivalent appearing as glucose in the portal vein was 49.7 +/- 7.2% for the slow starch and 48.2 +/- 7.5% for the rapid starch (P = 0.86). These values, corrected for the gut extraction of circulating [(13)C]glucose, became 66.4 +/- 5.6 and 65. 3 +/- 5.6%, respectively (P = 0.35). Isotope dilution data indicated that systemic appearance of exogenous [(13)C]glucose represented 62. 9 +/- 7.6 and 67.4 +/- 3.0% of the oral load for slow and rapid starch, respectively (P = 0.68). Arterial glucose utilization by the gut increased from 7.3 +/- 0.9 micromol x kg(-1) x min(-1) before the meal to 8.5 +/- 1.6 micromol x kg(-1) x min(-1) during absorption, independently of the nature of the starch. Thus splanchnic glucose metabolism was unaffected by the nature of starch ingested.     

Molecular mechanism of antidiabetic zinc–allixin complexes: regulations of glucose utilization and lipid metabolism

We previously reported new zinc complexes of allixin [bis(allixinato)zinc] and its derivative bis(thioallixin-N-methyl)zinc that demonstrated excellent antidiabetic activity in type 2 diabetic mellitus KKA(y) mice. However, the molecular mechanism of these complexes is not fully understood. Thus, we attempted to reveal the intracellular mechanism of these complexes in 3T3-L1 adipocytes. Both zinc complexes induced Akt/protein kinase B (Akt/PKB) phosphorylation. The phosphorylation of Akt/PKB enhanced glucose transporter 4 translocation to the plasma membrane; this in turn enhanced the glucose utilization in a dose- and time-dependent manner. Glucose utilization by the complexes depended on the intracellular zinc concentration. Moreover, zinc complexes suppressed the cyclic AMP dependent protein kinase mediated phosphorylation of hormone-sensitive lipase (HSL), leading to the inhibition of free fatty acid release from the 3T3-L1 adipocytes. Such responses were inhibited by wortmannin, suggesting that the suppression of HSL by zinc complexes was dependent in the phosphoinositide 3-kinase-Akt/PKB signaling cascade. On the basis of these results, we proposed that both zinc complexes activated the Akt/PKB-mediated insulin-signaling pathway and improved both glucose utilization and lipid metabolism.     

Recurrent seasonal changes in bacterial growth efficiency,metabolism and community composition in coastal waters

The microbial response to environmental changes in coastal waters of the eastern Cantabrian Sea was explored for four years by analysing a broad set of environmental variables along with bacterial community metabolism and composition. A recurrent seasonal cycle emerged, consisting of two stable periods, characterized by low bacterial metabolic activity (winter) from October to March, and high bacterial metabolic activity (summer) from May to August. These two contrasting periods were linked by short transition periods in April (T_A) and September (T_S). The phylogenetic groups Alphaproteobacteria and Bacteroidetes were dominant during winter and summer respectively, and their recurrent alternation was mainly driven by the bloom of eukaryotic phytoplankton before T_A and the bloom of prokaryotic phytoplankton before T_S. Bacterial growth efficiency remained high and stable during the winter and summer periods but dropped during the two short transition periods. Our results suggest that bacterial growth efficiency should be considered a very resilient property that reflects different stages in the adaptation of the bacterial community composition to the environmental changes occurring throughout the seasonal cycle in this coastal ecosystem.     

Transcriptional expression changes of glucose metabolism genes after exercise in thoroughbred horses

Physical exercise induces gene expression changes that trigger glucose metabolism pathways in organisms. In the present study, we monitored the expression levels of LDHA (lactate dehydrogenase) and GYS1 (glycogen synthase 1) in the blood, to confirm the roles of these genes in exercise physiology. LDHA and GYS1 are related to glucose metabolism and fatigue recovery, and these processes could elicit economically important traits in racehorses. We collected blood samples from three retired thoroughbred racehorses, pre-exercise and immediately after 30 min of exercise. We extracted total RNA and small RNA (≤ 200 nucleotide-long) from the blood, and assessed the expression levels of LDHA, GYS1, and microRNAs (miRNAs), by using qRT-PCR. We showed that LDHA and GYS1 were down-regulated, whereas eca-miR-33a and miR-17 were up-regulated, after exercise. We used sequences from the 3′ UTR of LDHA and GYS1, containing eca-miR-33a and miR-17 binding sites, to observe the down-regulation activity of each gene expression. We observed that the two miRNAs, namely, eca-miR-33a and miR-17, inhibited LDHA and GYS1 expression via binding to the 3′ UTR sequences of each gene. Our results indicate that eca-miR-33a and miR-17 play important roles in the glucose metabolism pathway. In addition, our findings provide a basis for further investigation of the exercise metabolism of racehorses.     

Zonal variability and seasonal changes of the content of glycogen and glucose in the Mytilus mantle

Glycogen and free-glucose content in the ventral, central and dorsal parts, as well as glucose-6-phosphate phosphatase activity in mantle of Mytilus galloprovincialis Lmk. were examined. The glycogen content of mantle did not manifest asymmetrical distribution among the three parts. In the period studied, the typical glycogen content profile variation was found, being maximum in July. The tissue free-glucose content was similar in each part, and the obtained seasonal variation profile was opposite to the glycogen content, reaching the minimum in July. For every part of mantle, free-glucose/glycogen ratio showed similar monthly profiles. In each part the 50% point was found in July. Glucose-6-phosphate phosphatase activity was not found in the mantle tissue.     

Rest-activity rhythms characteristics and seasonal changes in seasonal affective disorder

ABSTRACT

Identifying objectively measurable seasonal changes in 24-h activity patterns (rest-activity rhythms or RARs) that occur in seasonal affective disorder (SAD) could help guide research and practice towards new monitoring tools or prevention targets. We quantified RARs from actigraphy data using non-parametric and extended cosine based approaches, then compared RARs between people with SAD and healthy controls in the summer (n = 70) and winter seasons (n = 84). We also characterized the within-person seasonal RAR changes that occurred in the SAD (n = 19) and control (n = 26) participants who contributed repeated measures. Only controls had significant winter increases in RAR fragmentation (intra-daily variability; in controls mean winter-summer changes (log scale) = 0.05, 0.21 standard deviation, p = 0.03). In SAD participants only, estimated evening settling times (down-mesor) were an average of 30 min earlier in the winter compared with the summer (1-h standard deviation, p = 0.045). These RAR characteristics correlated with greater fatigue (Spearman r = 0.36) but not depression symptom severity. Additional research is needed to ascertain why healthy controls, but not people with SAD, appear to have increased RAR fragmentation in the winter. People with SAD lacked this increase in RAR fragmentation, and instead had earlier evening setting in the winter. Prospective and intervention studies with greater temporal resolution are warranted to ascertain how these seasonal behavioral differences relate to fatigue pathophysiology in SAD. Future research is needed to determine whether extending the winter active period, even in relatively fragmented bouts, could help reduce the fatigue symptoms common in SAD.     

Host utilization and seasonal occurrence of Dermacentor

A total of 3,235 Dermacentor variabilis (Say) specimens were collected from birds, mammals, and by dragging vegetation, and 2,683 D. albipictus (Packard) ticks were collected from deer from 1993 to 1996. Peak seasonal occurrence of adult D. variabilis was from May through July with a precipitous decrease in August. Nymphal D. variabilis populations peaked in June. Peak activity of larvae was bimodal, with one activity peak during late summer (September) and a second peak in winter or early spring. The raccoon, Procyon lotor (L.), was the principal host of adults followed by the Virginia opossum, Didelphis virginiana Kerr. Rodents and the eastern cottontail rabbit, Sylvilagus floridanus (J. A. Allen), were the primary hosts of nymphs. The marsh rice rat, Oryzomys palustris (Harlan), was the principal host of larvae followed by the pine vole, Microtus pinetorum (Le Conte), and white-footed mouse, Peromyscus leucopus (Rafinesque). All stages of D. albipictus were found only on white-tailed deer, Odocoileus virginianus (Zimmermann). Numbers of adult and nymphal D. albipictus peaked in November, whereas larvae peaked in September.     

Carbohydrate and amino acid metabolism in Tuber borchii mycelium during glucose utilization: a (13)C NMR study

The metabolism of [1-13C]glucose in the vegetative mycelium of the ectomycorrhizal ascomycete Tuber borchii was studied in order to characterize the biochemical pathways for the assimilation of glucose and amino acid biosynthesis. The pathways were characterized using nuclear magnetic resonance spectroscopy in conjunction with [1-13C]glucose labeling. The enzymes of mannitol cycle and ammonium assimilation were also evaluated. The majority of the 13C label was incorporated into mannitol and this polyol was formed via a direct route from absorbed glucose. Amino acid biosynthesis was also an important sink of assimilated carbon and 13C was mainly incorporated into alanine and glutamate. From this intramolecular 13C enrichment, it is concluded that pyruvate, arising from [1-13C]glucose catabolism, was used by alanine aminotransferase, pyruvate dehydrogenase and pyruvate carboxylase before entering the Krebs cycle. The transfer of 13C-labeled mycelium on [12C]glucose showed that mannitol, alanine, and glutamate carbon were used to synthesize glutamine and arginine that likely play a storage role.