Enhancing Effect Of Glucose Research Articles

Effects of different glucose concentrations on the leptin signaling pathway in MCF-7 and T47D breast cancer cells.

Leptin activates multiple intracellular signaling pathways, including JAK/STAT, by binding to its receptor. Leptin is also an important regulator of glucose homeostasis. Although both glucose and leptin increase breast cancer cell proliferation in vitro, whether the enhancing effect of glucose on the proliferation of breast cancer cells is mediated by the leptin signaling pathway is not known. The aim of this study was to investigate the effect of different glucose concentrations on the leptin signaling pathway in MCF-7 and T47D breast cancer cells. MCF-7 and T47D cell proliferation in different glucose concentrations (2.5 mM, 5 mM, 25 mM, or 50 mM) were assayed using CCK-8 assay. Leptin, leptin receptors (ObR, ObRb) as well as STAT3 mRNA and protein levels in both cell lines in different glucose concentrations were examined by RT-PCR and western blot, respectively. Incubation in 2.5 mM, 5 mM, 25 mM, or 50 mM glucose for 72h significantly increased the proliferation of both MCF-7 and T47D cells compared to 0 mM glucose incubated cells (P<0.001). mRNA levels of leptin, ObR, ObRb or STAT3 in 2.5 mM, 5 mM, 25 mM, or 50 mM glucose incubated cells were not significantly different in both cell lines compared to 0 mM (p>0.05). However, ObR protein levels in MCF-7 cells incubated in 25 mM glucose was significantly lower compared to 0 mM glucose by western blot (p<0.05). Our data suggest that the enhancing effect of glucose on breast cancer cell proliferation is not mediated by the JAK/STAT pathway.

Impact of L-FABP and glucose on polyunsaturated fatty acid induction of PPARα-regulated β-oxidative enzymes

Liver fatty acid binding protein (L-FABP) is the major soluble protein that binds very-long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) in hepatocytes. However, nothing is known about L-FABP's role in n-3 PUFA-mediated peroxisome proliferator activated receptor-α (PPARα) transcription of proteins involved in long-chain fatty acid (LCFA) β-oxidation. This issue was addressed in cultured primary hepatocytes from wild-type, L-FABP-null, and PPARα-null mice with these major findings: 1) PUFA-mediated increase in the expression of PPARα-regulated LCFA β-oxidative enzymes, LCFA/LCFA-CoA binding proteins (L-FABP, ACBP), and PPARα itself was L-FABP dependent; 2) PPARα transcription, robustly potentiated by high glucose but not maltose, a sugar not taken up, correlated with higher protein levels of these LCFA β-oxidative enzymes and with increased LCFA β-oxidation; and 3) high glucose altered the potency of n-3 relative to n-6 PUFA. This was not due to a direct effect of glucose on PPARα transcriptional activity nor indirectly through de novo fatty acid synthesis from glucose. Synergism was also not due to glucose impacting other signaling pathways, since it was observed only in hepatocytes expressing both L-FABP and PPARα. Ablation of L-FABP or PPARα as well as treatment with MK886 (PPARα inhibitor) abolished/reduced PUFA-mediated PPARα transcription of these genes, especially at high glucose. Finally, the PUFA-enhanced L-FABP distribution into nuclei with high glucose augmentation of the L-FABP/PPARα interaction reveals not only the importance of L-FABP for PUFA induction of PPARα target genes in fatty acid β-oxidation but also the significance of a high glucose enhancement effect in diabetes.

Dose–response investigation into glucose facilitation of memory performance and mood in healthy young adults

It has been suggested that the memory enhancing effect of glucose follows an inverted U-shaped curve, with 25 g resulting in optimal facilitation in healthy young adults. The aim of this study was to further investigate the dose dependency of the glucose facilitation effect in this population across different memory domains and to assess moderation by interindividual differences in glucose regulation and weight. Following a double-blind, repeated measures design, 30 participants were administered drinks containing five different doses of glucose (0 g, 15 g, 25 g, 50 g, and 60 g) and were tested across a range of memory tasks. Glycaemic response and changes in mood state were assessed following drink administration. Analysis of the data showed that glucose administration did not affect mood, but significant glucose facilitation of several memory tasks was observed. However, dose-response curves differed depending on the memory task with only performance on the long-term memory tasks adhering largely to the previously observed inverted U-shaped dose-response curve. Moderation of the response profiles by interindividual differences in glucose regulation and weight was observed. The current data suggest that dose-response function and optimal dose might depend on cognitive domain and are moderated by interindividual differences in glucose regulation and weight.

P3b versus P3a: an event-related potential investigation of the glucose facilitation effect

The ingestion of a glucose containing drink has been shown to improve performance on a variety of cognitive tasks. There is debate, however, as to whether glucose especially benefits hippocampal memory functioning or whether it has a more global effect on attentional systems. The present study used event related potential methodology (ERPs) to investigate further glucose-mediated cognitive processes. Each participant acted as his/her own control in a repeated measures design, receiving one of two possible treatments (25 g glucose vs. placebo) in a counterbalanced order. After a two hour fasting period participants completed a visual three-stimulus oddball task. This paradigm involves an individual detecting an infrequent target stimulus randomly embedded in a train of repetitive background or standard stimuli. Detection of the target results in a large P3b ERP component (memory updating effect). The infrequent presentation of a novel and irrelevant stimulus, randomly interspersed with the target and standard stimuli, generates a P3a response (orientation of attention effect). These components were used as markers to establish whether the glucose enhancement effect was restricted to the neuro-cognitive processes related to memory. Consistent with behavioural work, glucose moderated the magnitude and latency of the P3b ERP component. However, glucose also interacted with attentional systems (P3a and an earlier P2), although this effect was non-significant. This work converges with recent fMRI findings indicating the sensitivity of the medial-temporal lobes and the pre-frontal cortex to glucose administration.

The facilitative effects of glucose ingestion on memory retrieval in younger and older adults: is task difficulty or task domain critical?

The ingestion of a glucose-containing drink has been shown to improve cognitive performance, particularly memory functioning. However, it remains unclear as to the extent to which task domain and task difficulty moderate the glucose enhancement effect. The aim of this research was to determine whether boosts in performance are restricted to particular classes of memory (episodic v. semantic) or to tasks of considerable cognitive load. A repeated measures (25 g glucose v. saccharin), counterbalanced, double-blind design was used with younger and older adults. Participants performed a battery of episodic (e.g. paired associate learning) and semantic memory (e.g. category verification) tasks under low and high cognitive load. Electrophysiological measures (heart rate and galvanic skin response) of arousal and mental effort were also gathered. The results indicated that whilst glucose appeared to aid episodic remembering, cognitive load did not exaggerate the facilitative effect. For semantic memory, there was little evidence to suggest that glucose can boost semantic memory retrieval even when the load was manipulated. One exception was that glucose facilitated performance during the difficult category fluency task. Regardless, the present findings are consistent with the domain-specific account in which glucose acts primarily on the hippocampal region, which is known to support episodic memory. The possible contribution of the hippocampus in semantic memory processing is also discussed.

The Impact of Age and Task Domain on Cognitive Performance: A Meta-Analytic Review of the Glucose Facilitation Effect

AbstractConsiderable research has been devoted to the issue of whether the ingestion of glucose enhances cognitive performance in both younger and older adults. However, it has proven difficult to draw firm conclusions from this literature due to the diversity of methodologies that have been used, and it is therefore still unclear what factors might moderate the facilitative effect. The present study investigates methodological variations and their impact on the magnitude of the glucose enhancement effect. In particular, age group (young vs. old) and task domain (memory vs. nonmemory tasks) were considered as moderator variables. In addition, differences in experimental design, glucose dose and fasting regime were examined. The effect sizedwas extracted from studies comparing cognitive performance after the ingestion of either a glucose or control solution. Subsequent meta-analyses were conducted (using the procedures outlined by Hedges &amp; Olkin, 1985) to examine potential moderators. A moderate overall effect size was found (d= 0.56), which clearly demonstrated the value of glucose ingestion as a cognitive enhancer. However, this effect size was not representative of the 104 individual effect sizes reported. Secondary analyses found larger effect sizes for memory compared to nonmemory tasks. Unexpectedly, no evidence was provided for greater beneficial effects of glucose on cognitive performance for older compared to younger adults. The impact of other methodological variables and the need for further exploration in an elderly population are discussed.

Incomplete intestinal absorption of fructose.

Intestinal D-fructose absorption in 31 children was investigated using measurements of breath hydrogen. Twenty five children had no abdominal symptoms and six had functional bowel disorders. After ingestion of fructose (2 g/kg bodyweight), 22 children (71%) showed a breath hydrogen increase of more than 10 ppm over basal values, indicating incomplete absorption: the increase averaged 53 ppm, range 12 to 250 ppm. Four of these children experienced abdominal symptoms. Three of the six children with bowel disorders showed incomplete absorption. Seven children were tested again with an equal amount of glucose, and in three of them also of galactose, added to the fructose. The mean maximum breath hydrogen increases were 5 and 10 ppm, respectively, compared with 103 ppm after fructose alone. In one boy several tests were performed with various sugars; fructose was the only sugar incompletely absorbed, and the effect of glucose on fructose absorption was shown to be dependent on the amount added. It is concluded that children have a limited absorptive capacity for fructose. We speculate that the enhancing effect of glucose and galactose on fructose absorption may be due to activation of the fructose carrier. Apple juice in particular contains fructose in excess of glucose and could lead to abdominal symptoms in susceptible children.

Difference in calcium dependency of insulin, glucagon and somatostatin secretion in response to glibenclamide in perfused rat pancreas.

The extracellular calcium requirements for insulin, glucagon and somatostatin release induced by 1 microgram/ml of glibenclamide have been compared in the perfused, isolated rat pancreas. In the absence of glucose, the drug evoked insulin release equally well at physiological (2.6 mmol/l) and low (0.25 mmol/l) levels of total calcium. In contrast, glibenclamide evoked somatostatin release at 2.6 but not at 0.25 mmol/l of calcium. At 2.6 mmol/l of calcium, glibenclamide evoked bimodal effects (stimulation followed by inhibition) on glucagon secretion. At 0.25 mmol/l of calcium, basal secretory rates of glucagon were elevated and a small stimulatory effect of glibenclamide was seen. Addition of 0.5 mmol/l of EGTA to media with low calcium concentrations uniformly abolished the A, B and D cell secretory responses to glibenclamide. The possible modulation of calcium dependency by a non-stimulatory concentration of glucose was tested by its addition at 3.3 mmol/l to the perfusion media. Glucose enhanced glibenclamide-induced insulin secretion, both at 0.25 and 2.6 mmol/l of calcium. However, at 0.25 mmol/l of calcium, the enhancing effect of glucose was more pronounced than at 2.6 mmol/l. At 2.6 mmol/l of calcium, glucose diminished the somatostatin and abolished the glucagon response to glibenclamide. At 0.25 mmol/l of calcium, glucose did not influence somatostatin release while the presence of the sugar diminished basal and glibenclamide-induced glucagon secretion. The present data confirm the requirement of extracellular calcium for A, B and D cell secretion, demonstrating different calcium dependencies for the cell types and indicate that this dependency can, in part, be modulated by glucose.

Regulation of glycogen synthase activity in the isolated mouse soleus muscle effect of insulin, epinephrine, glucose and anti-insulin receptor antibodies

The effects of insulin, epinephrine, glucose and anti-insulin receptor antibodies on enzymes involved in the regulation of glycogen synthesis were investigared in the isolated mouse soleus muscle. Insulin maximally increased the percentage of glycogen synthase active form after 15 min in the absence of glucose in the extracellular medium; half-maximal and maximal effects were obtained with 1.5 and 33 nM insulin, respectively. The basal percentage of glycogen phosphorylase active form was not altered by insulin. Antibodies to the insulin receptor had similar effects to those of insulin on both enzymes. The percentage of glycogen synthase active form was maximally decreased and that of phosphorylase maximally increased after a 2 min exposure to epinephrine in the absence of extracellular glucose. Glucose alone had no effect on muscle glycogen synthase. When muscles were incubated with insulin (33 nM) plus glucose (20 mM) for 5–10 min, the increase in the percentage of glycogen synthase active form was greater than with insulin alone. This enhancing effect of glucose on insulin activation of glycogen synthase disappeared after 20 min. The results suggest the existence of two mechanisms whereby insulin activates muscle glycogen synthase. The main effect is operative in the absence of extracellular glucose and occurs at insulin concentrations close to the physiological range. The other effect requires glucose and may result from the stimulation by insulin of glucose transport and/or metabolism.

Energy metabolism and repair of U.V. damage in Saccharomyces. 1. The effect of glucose on recovery of U.V.-sensitive mutants.

SummaryLiquid-holding recovery in Saccharomyces was found to depend on glucose concentration during pre-irradiation treatment or during the liquid-holding period in the wild type and in mutant strains rs1rs1, rs2rs2, rs3−2rs3−2. The maximum glucose enhancement effect on survival was about 15 per cent in wild-type, 40 per cent in rs1rs1, 20 per cent in rs2rs2 and 3 per cent in rs3−2rs3−2 mutants at a buffer concentration of 4 × 10−10 g glucose per cell. Concentrations greater than 10−7 g glucose per cell cause a decreasing effect on liquid-holding recovery. The results are discussed in view of different energy pathways and the lack of repair capacities in the strains used.

Folic Acid Absorption in Man: Enhancing Effect of Glucose

Folic acid absorption in the human jejunum was measured using tritiated pteroylglutamic acid in a triple lumen tube perfusion system. A comparison was made between absorption of folic acid in isotonic saline perfused in 11 subjects, and folic acid in isosmotic glucose and saline perfused in 10 subjects. Five subjects received both solutions. The addition of glucose resulted in a marked increase in folic acid absorption as well as in sodium and water absorption. There was a significantly positive correlation between folate absorption and water absorption for all subjects.

Effect of phlorizin on the in vitro release of histamine from lung tissue.

AbstractHistamine release was induced from sensitized guinea‐pig lung tissue by antigen, and from non‐sensitized rat lung tissue by compound 48/80. Phlorizin (10‐3M) had no apparent inhibitory effect on the histamine‐releasing reactions when elicited under nitrogen in the presence of 5.6 × 10‐3M glucose. When the glucose concentration was decreased to 7 × 10‐4M, phlorizin (10‐3M) inhibited histamine release under nitrogen in both reactions, to the same extent as did nitrogenation in the absence of glucose. Under nitrogen, the enhancing effect of glucose was progressively inhibited by increasing concentrations of phlorizin. In both reactions, its inhibitory effect decreased with rising glucose concentration. The results are interpreted to indicate that phlorizin inhibits histamine release mainly by inhibiting the transport of glucose.