Rise In Fructose Research Articles

The Role of Melatonin in the Pathogenesis of Hypertension in Rats With Metabolic Syndrome

Melatonin, the primary hormone of the pineal gland, is a known modulator of various physiological processes. The aim of this study was to evaluate the role of melatonin in the pathogenesis of hypertension in rats with metabolic syndrome and to assess whether melatonin supplementation prevents the development of hypertension in this model. Twenty male Sprague-Dawley (SD) rats were fed either a high fructose diet (n = 10) or a regular diet (control; n = 10) for 5 weeks. Urinary excretion of 6-hydroxymelatoninsulfate (a metabolite of melatonin) was measured at the beginning and the end of the study. An additional 20 SD rats were fed with the same diets but with a supplementation of melatonin (30 mg/kg/day) in their drinking water. Blood pressure (BP) was measured every week. BP increased significantly in rats fed with a high fructose diet and remained unchanged in the control group. The BP rise was associated with a significant decrease in melatonin secretion during sleep. Melatonin supplementation prevented the BP rise in fructose fed rats. BP increased by 14.6 +/- 1.0 mm Hg in the fructose fed rats, whereas it increased by only 3 +/- 2.6 mm Hg in rats fed with fructose and melatonin (P < 0.001 between groups). Melatonin secretion decreased in fructose fed rats that developed hypertension. Administration of melatonin blunted this BP rise. These data suggested that melatonin plays a role in the pathogenesis of hypertension in rats with metabolic syndrome.

Dynamics of Early Fermentation of Italian Ryegrass (Lolium multiflorum Lam.) Silage

The dynamics of fermentation were studied with Italian ryegrass ensiled in the laboratory silos. The silos were kept in the room set at 25°C, and then were opened on 0.5, 1, 2, 3, 5, 7 and 14 days after ensiling, respectively. The samples were taken from three silos at each sampling time for chemical analyses. Mono-and disaccharides composition was determined for glucose, fructose and sucrose by high performance liquid chromatography. The Italian ryegrass silage succeeded to achieve lactate type fermentation; high values of lactic acid (85.83 g/kg) and lactic acid/acetic acid at the end of ensiling (14 day), low values of pH (3.74), acetic acid (5.38 g/kg), ethanol (19.20 g/kg) and NH3-N/Total N (75.84 g/kg), no or only small amounts of butyric acid, valeric acid and propionic acid. The fermentation dynamics showed a fast and large pH decrease caused by a fast and large production of lactic acid during the first 5 days. Mono-and disaccharides composition largely decreased within initial 0.5 day (12 h) of ensiling. Sucrose disappeared rapidly within initial 0.5 day of ensiling, and fructose and glucose contents showed an initial rise during ensiling, and then decreased gradually. These indicated that the enzymes of plant tissue were active within 2 days of ensiling, which caused the initial rise in fructose and glucose from the hydrolysis of sucrose and fructans. After 5 days of ensilage, glucose was consumed completely, suggesting that glucose was the first fermentation substrate. After 2 days of ensiling, sum amounts of lactic acid and remaining mono-and disaccharides proved to be larger than the quantity of mono-and disaccharides in the initial grass. From the facts mentioned above, it was suggested that considerable amounts of lactic acid were produced from some other substrate such as fructans than initial mono-and disaccharides. (Asian-Aust. J. Anim. Sci. 2002. Vol 15, No. 11 : 1606-1610)

Vanadate treatment rapidly improves glucose transport and activates 6-phosphofructo-1-kinase in diabetic rat intestine

The effect of oral vanadate on intestinal sodium-dependent glucose transport and 6-phosphofructo-1-kinase (EC 2.7.1.11) activity was examined in male Sprague-Dawley rats following a 30-day period of non-treated streptozotocin-induced diabetes. Non-treated diabetic rats were hyperglycaemic and demonstrated increased intestinal sodium-dependent glucose transport and Na,K-ATPase activity compared with controls. These increases were associated with a significant decrease in the total activity and activity ratios (activity at 0.5 mmol/l fructose 6-phosphate at pH 7.0/activity at pH 8.0) of intestinal 6-phosphofructo-1-kinase and decreased levels of fructose 2,6-bisphosphate. Supplementation of drinking water with vanadate (0.5 mg/ml) resulted in a rapid decline in blood glucose levels to a slightly hyperglycaemic level. Jejunal glucose transport and Na,K-ATPase activity were normalized after 48 h of vanadate treatment. In contrast, ileal glucose transport was significantly reduced 12 h following beginning vanadate treatment even though Na,K-ATPase activity did not normalize until 36 h later. Km was significantly decreased in both jejunum and ileum by vanadate treatment indicating an increased affinity of the sodium-dependent intestinal glucose transporter for glucose. 6-phosphofructo-1-kinase total activity and susceptibility to ATP inhibition was completely restored after 12 h of vanadate treatment. This increase was associated with a rise in fructose 2,6-bisphosphate levels. Fasting rats for 12 h had no effect on glucose transport or 6-phosphofructo-1-kinase activity, indicating the anorectic effect of vanadate was not responsible for changes in either parameter. In contrast, cycloheximide prevented both the rise in 6-phosphofructo-1-kinase activity and the rise in fructose 2,6-bisphosphate levels, and the subsequent reduction in glucose transport, indicating a requirement for protein synthesis. The removal of vanadate resulted in an immediate return to pre-treatment blood glucose levels. In contrast, intestinal glucose transport and 6-phosphofructo-1-kinase activity remained at treatment levels up until 72 h, indicating that oral vanadate treatment can have prolonged beneficial effects on intestinal function. In conclusion, the treatment of streptozotocin-induced diabetic rats with oral vanadate results in an activation of 6-phosphofructo-1-kinase coupled with a normalization of intestinal sodium-dependent glucose transport. Vanadate may thus have a beneficial effect on intestinal function and may prove useful as oral adjunctive diabetic therapy.

Incorporation of fructose by the mouse embryo: Effect on preimplantation development

Abstract Culture of outbred strains of 1-cell mouse embryos in glucose-containing medium was found to lead to cleavage arrest. In addition, glycogen accumulation occured during the later stages. Exchange of glucose with fructose in media may improve embryo development as it enters metabolic pathways through a different pathway. We therefore tried to improve embryo development in vitro by culturing 1-cell mouse embryos in M16 medium containing fructose instead of glucose (M16F-G). One-cell OF1 embryos, cultured in fructose-containing medium overcame cleavage arrest at the 2-cell stage (blastocyst formation: 53 vs 2%). A significant increase in blastocyst formation was also observed for DDK mouse strain. Fructose was incorporated into the 1-cell mouse embryo at the same rate as glucose (30 fmoles/zygote/h), depending upon the external concentration. Radiolabeling was detected in CO 2 and proteins, indicating that fructose was converted and metabolized. At this stage, glucose did not compete with fructose uptake. But at the blastocyst stage, fructose incorporation increased tenfold and was inhibited by high levels of glucose. We propose that addition of fructose may turn on glycolysis by means of a rise in fructose 6 phosphate, a de-inhibitor of P-fructokinase. This may in turn be responsible for the increase in blastocyst development and hatching rates, as observed in some strains.

Glycolysis at the climacteric of bananas

This work was carried out to investigate the relative roles of phosphofructokinase and pyrophosphate-fructose-6-phosphate 1-phosphotransferase during the increased glycolysis at the climacteric in ripening bananas (Musa cavendishii Lamb ex Paxton). Fruit were ripened in the dark in a continuous stream of air in the absence of ethylene. CO2 production, the contents of glucose 6-phosphate, fructose 6-phosphate, fructose 1,6-bisphosphate, phosphoenolpyruvate and PPi; and the maximum catalytic activities of pyrophosphate-fructose-6-phosphate 1-phosphotransferase, 6-phosphofructokinase, pyruvate kinase and phosphoenolpyruvate carboxylase were measured over a 12-day period that included the climacteric. Cytosolic fructose-1,6- bisphosphatase could not be detected in extracts of climacteric fruit. The peak of CO2 production was preceded by a threefold rise in phosphofructokinase, and accompanied by falls in fructose 6-phosphate and glucose 6-phosphate, and a rise in fructose 1,6-bisphosphate. No change in pyrophosphate-fructose-6-phosphate 1-phosphotransferase or pyrophosphate was found. It is argued that phosphofructokinase is primarily responsible for the increased entry of fructose 6-phosphate into glycolysis at the climacteric.

Cyclic AMP regulation of fructose metabolism in germinating Pilobolus longipes spores

Dormant Pilobolus longipes spores metabolized fructose primarily to ethanol, CO 2, and trehalose. Cyclic AMP-induced spore activation was accompanied by a large stimulation of glycolytic activity. Mobilization of reserves, which was cyclic AMP dependent, accounted for a portion of the glycolytic product. The remaining product was derived from exogenous fructose. Increases in both fructose transport activity and hexose 6-phosphate levels were associated with 6-deoxyglucose-induced spore activation. Phosphofructokinase-1 activity in spore extracts was almost totally dependent upon fructose, 2,6-bisphosphate. High fructose 2,6-bisphosphate levels were correlated with rapid fructose metabolism. However, fructose alone caused a rise in fructose 2,6-bisphosphate content (sufficient to fully stimulate phosphofructokinase-1 activity) but there was no concurrent stimulation of glycolysis. These results suggest that glycolytic rates are determined mainly by hexose 6-phosphate levels and that cyclic AMP regulation of transport is an important determinant of hexose 6-phosphate concentration.

Epidermal growth factor and 12-O-tetradecanoylphorbol 13-acetate stimulate lactate production and the pentose phosphate pathway in freshly isolated rat hepatocytes.

Epidermal growth factor (EGF) and tetradecanoylphorbol acetate (TPA) rapidly stimulated the production of lactate by hepatocytes isolated from fed rats. Our results indicate that enzymes of both glycolysis and the pentose phosphate pathway are involved in these actions. EGF stimulated CO2 release from the 1-position of glucose, and caused a small but significant increase in pyruvate kinase activity. In addition, EGF caused a rise in fructose 1,6-bisphosphate and fructose 2,6-bisphosphate concentrations, indicating activation of phosphofructokinase. TPA did not alter the concentrations of these sugar phosphates, but did cause an increased lactate production and CO2 production from the 1-position of glucose similar to EGF. Furthermore, the EGF stimulation of lactate formation was independent of the presence of medium Ca2+. Phenylephrine stimulation of this process, in parallel incubations, was entirely dependent upon the presence of Ca2+ in the medium. We conclude that EGF stimulates glycolysis and the pentose phosphate pathway in isolated hepatocytes from fed rats. The duplication of these actions by TPA suggests that protein kinase C is a mediator of EGF action in hepatocytes.

Fructose 2,6‐Bisphosphate Changes in Rat Brain During Ischemia

Brain ischemia was produced by bilateral ligation of the common carotid arteries of spontaneously hypertensive rats. The concentrations of fructose 2,6-bisphosphate and other glycolytic intermediates as well as of pyridine and adenine nucleotides were measured in frozen brain samples. In contrast to the decrease reported in hepatocytes under anoxic conditions, the fructose 2,6-bisphosphate content was increased by 20-30% during the early stages of ischemia. Elevation in fructose 1,6-bisphosphate level and lactate formation followed the rise in fructose 2,6-bisphosphate content, a finding suggesting that this compound plays a key role in the compensatory acceleration of glycolysis under ischemic conditions in vivo.

PH sensitivity of the thrombin-induced rise in fructose 2,6-bisphosphate content of human platelets

The stimulation of human platelets with thrombin results in a rapid and sustained increase in the fructose 2,6-bisphosphate content which may play an important role in the potentiation of glycolytic flux induced by the agonist. The investigation of the effect of pH on thrombin-induced rise in platelet fructose 2,6-bisphosphate content is reported here. The results indicate that the early intracellular alkalinization which follows platelet stimulation may contribute to mediate the positive effect of thrombin on the regulatory metabolite.

A Rapid Increase in Spinach Leaf Fructose 2,6-Bisphosphate Occurs during a Light to Dark Transition

Spinach leaf fructose 2,6-bisphosphate levels increase rapidly during the first 15 minutes of a normal dark period followed by a gradual decline during the next 5 hours. The regulatory mechanism responsible for the dark-induced rise in fructose 2,6-bisphosphate levels can be counteracted by a brief exposure to light intensities greater than 1 microeinstein per square meter per second.

Regulation of fructose 2,6-bisphosphate concentration in white adipose tissue.

Injection of insulin to fed rats diminished the concentration of fructose 2,6-bisphosphate in white adipose tissue. Incubation of epididymal fat-pads or adipocytes with insulin stimulated lactate release and sugar detritiation and also decreased fructose 2,6-bisphosphate concentration. Such a decrease was, however, not observed in fat-pads from starved or alloxan-diabetic rats. Incubation of adipocytes from fed rats with various concentrations of glucose or fructose led to a dose-dependent rise in fructose 2,6-bisphosphate which correlated with lactate output and detritiation of 3-3H-labelled sugar. In adipocytes from fed rats, palmitate stimulated the detritiation of [3-3H]glucose without affecting lactate production and fructose 2,6-bisphosphate concentration. Incubation of epididymal fat-pads from fed rats in the presence of antimycin stimulated lactate output but decreased fructose 2,6-bisphosphate concentration. Changes in lipolytic rates brought about by noradrenaline, insulin, adenosine and corticotropin in adipocytes from fed rats were not related to changes in fructose 2,6-bisphosphate or to rates of lactate output. In fed rats, the activity of 6-phosphofructo-2-kinase was not changed after treatment of adipocytes with insulin, noradrenaline or adenosine. It is suggested that the decrease in fructose 2,6-bisphosphate concentration observed after insulin treatment can be explained by the increase in sn-glycerol 3-phosphate, an inhibitor of 6-phosphofructo-2-kinase.

Changes in key regulatory enzymes of hepatic carbohydrate metabolism after glucose loading of starved rats

When glucose was given to starved rats there was an increase in both 6-phosphofructo 2-kinase and pyruvate kinase activity and a decrease in fructose 2,6-bisphosphatase activity 30 min and 60 min later. These changes were accompanied by an increase in glycogen deposition and by modest, but significant increases in fructose 2,6-bisphosphate levels at the same time. Metabolite measurements indicated that flux through 6-phosphofructo 1-kinase and pyruvate kinase were increased. These results suggest that although glycogen deposition may occur via the gluconeogenic pathway, glycolysis is activated at the same time by changes in the phosphorylation state of key regulatory enzymes as well as by the small rise in fructose 2,6-bisphosphate.

Evidence for Control of Carbon Partitioning by Fructose 2,6-Bisphosphate in Spinach Leaves

Excision of spinach (Spinacia oleracea L.) leaves had no effect on photosynthetic rates, but altered normal carbon partitioning to favor increased formation of starch and decreased formation of sucrose. The changes were evident within 2 hours after excision. Concurrently, leaf fructose-2,6-bisphosphate content increased about 5-fold (from 0.1 to 0.5 nanomoles per gram fresh weight). The activities of sucrose-P synthase and cytoplasmic fructose 1,6-bisphosphatase in leaf extracts remained constant during the time period tested. It is postulated that the rise in fructose 2,6-bisphosphate was responsible for the change in carbon partitioning.

Adaptive changes of phosphofructokinase and aldolase in adipose tissue.

The activity of several enzymes of the glycolytic pathway was investigated in rat epididymal adipose tissue. Determination of phosphofructokinase and aldolase activity with an improved assay involving homogenization of the tissue in the presence of fructose 6‐phosphate showed that the activity of aldolase is in the same range or lower than that of hexokinase and phosphofructokinase. Both aldolase and phosphofructokinase exhibited an adaptive behavior. The activity at optimal assay conditions decreased in fasting or alloxan diabetic rats and rebounded on refeeding or upon treatment of diabetic rats with insulin. These changes are similar to those of hexobase and glucose‐6‐phosphate dehydrogenase, whereas the activity of pyruvate kinase was not influenced by these situations. Changes in the steady state concentrations of glycolytic intermediates in vivo provided further evidence that the activity of aldolase may intluence the rate of glycolysis in adipose tissue. A rise in fructose 1,6‐bisphosphate concentration relative to that of fructose 6‐phosphate was observed, especially in conditions of increased glucose flow. A rise in both fructose &amp;phosphate and fructose 1,6‐bisphosphate was observed in diabetic rats.The pattern of activities of glycolytic enzymes and of metabolite concentrations in adipose tissue is compared with that in other tissues, and the regulatory characteristics of glycolysis peculiar to adipose tissue are discussed.

Effects of High Levels of Exogenous Testosterone Propionate on Bovine Semen

In a 16-month old inbred bull, supplementary testosterone propionate given at 100 mg/day for 12 wk caused a decrease in the number of tailless sperm and an increase in the number of coiled-tailed sperm. In another inbred bull 28 months of age, 200 mg/day caused the production of sperm with abnormal heads, midpieces, and tails. Both levels of the hormone disrupted and partially inhibited spermatogenesis, and caused a rise in fructose and citric acid in the semen.

Role of enzymes in homeostasts—VI. Effect of triamcinolone and other steroids on enzymes involved in gluconeogenesis

In view of the reports that adrenocorticosteroids induced de novo synthesis of enzymes involved in gluconeogenesis, systematic studies were carried out to compare the potency of the various steroids and to establish the smallest dose necessary and shortest time required to detect enzyme synthesis for the key hepatic gluconeogenic enzymes, glucose 6-phosphatase and fructose 1,6-diphosphatase. The potency of triamcinolone, cortisone, hydrocortisone, and methylprednisolone (Medrol) as inducers of the gluconeogenic enzymes was compared in a 3-day injection schedule in rats and it was found that triamcinolone was the most effective inducer. Dose-response studies showed that daily injections of 10 mg of cortisone i.m. for 5 days or 1 mg of triamcinolone i.p. for 3 days achieved the highest increases in hepatic enzyme activities and nitrogen and glycogen content. In an effort to achieve a more rapid induction in enzyme synthesis cortisone and triamcinolone (25 mg/100 g) were injected i.p. Both steroids brought about a rapid rise in fructose 1,6-diphosphatase activity (128–145%) in 4–6 hr. Only triamcinolone, however, was capable of causing a significant increase in glucose 6-phosphatase activity during the same period. Further dose-response studies with triamcinolone revealed that a single i.p. dose of 0–25 mg/100 g was sufficient to induce statistically significant increases in hepatic glucose 6-phosphatase (140%) and in fructose 1,6-diphosphatase (159%) activity in 24 hr. A dose of 0.5 mg was capable of causing a statistically significant rise (117–121%,) in hepatic gluconeogenic enzyme activity in 6 hr. Since rapid increases in liver glucose 6-phosphatase and fructose 1,6-diphosphatase activity can be induced by triamcinolone administration, it appears that the mechanism of effect of the gluconeogenic corticosteroid hormones at the molecular level entails an early stepping up of the rate of synthesis of these key gluconeogenic enzymes.