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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin stimulation of hydrogen peroxide production by rat epididymal fat cells was investigated by studying the oxidation of formate to CO2 by endogenous catalase. Under optimal concentrations of formate (0.1 to 1 mM) and glucose (0.275 mM), insulin stimulated formate oxidation 1.5- to 2.0-fold. Inhibitors of catalase activity, including nitrite and azide, inhibited both basal and insulin-stimulated formate oxidation at concentrations that did not interfere with insulin effects on glucose C-1 oxidation or glucose H-3 incorporation into lipids. The addition of exogenous catalase increased formate oxidation only slightly, while exogenous H2O2 (0.5 mM) stimulated formate oxidation by endogenous catalase strongly. These data indicate that the insulin-stimulated H2O2 production was intracellular. Insulin dose-response curves for formate oxidation were identical with those for glucose H-3 incorporation into lipids. The dependence of relative insulin effects on the logarithm of the glucose concentration was bell-shaped for formate oxidation and correlated highly with the coresponding dependences of glucose C-1 oxidation and glucose H-3 incorporation into lipids. This suggests that insulin stimulation of intracellular H2O2 production is linked to glucose metabolism. Since it is known that extracellular H2O2 can mimic insulin in several respects, these observations suggest that H2O2 may act as a "second messenger" for the observed effects of insulin.
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PMID:Insulin-stimulated intracellular hydrogen peroxide production in rat epididymal fat cells. 42 81

1. The effect of dinitrophenol on the metabolism of glucose labelled with (14)C and tritium by epididymal fat-pad segments from fed rats was studied. Dinitrophenol at concentrations of 0.1-0.3mm: (a) had little effect on glucose utilization; (b) depressed synthesis of fatty acids and greatly increased that of lactate; (c) increased the T/(14)C ratio in fatty acids synthesized from [U-(14)C,3-T]glucose and decreased that in fatty acids synthesized from [U-(14)C,4-T]glucose; (d) abolished randomization of (14)C from [6-(14)C]glucose in lactate. 2. Dinitrophenol stimulated oxidation of pyruvate and greatly inhibited the oxidation of lactate. It inhibited lipogenesis from pyruvate and lactate. 3. From the isotope data it was calculated that: (a) dinitrophenol stimulates oxidation via the tricarboxylic acid cycle three- to six-fold; (b) dinitrophenol depresses markedly the operation of the pentose cycle; (c) in the presence of dinitrophenol, NADPH formed in the pentose cycle provides all the hydrogen equivalents for fatty acid reduction, whereas, in its absence, NADPH provides 50-70% of the hydrogen equivalents; (d) in the presence of dinitrophenol, there is an excess of ATP produced in the cytoplasm, which flows into the mitochondria. A reverse flow operates in the absence of dinitrophenol. 4. A balance of formation and utilization of reduced nicotinamide nucleotides in the cytoplasm was established. With dinitrophenol there is some excess of NADH. There are indications that this excess may be transferred into mitochondria in the form of malate. 5. Our results are interpreted to indicate the absence from adipose tissue of the alpha-glycerophosphate shuttle for transferring reducing equivalents from the cytoplasm to mitochondria. 6. The effects of dinitrophenol are accounted for in terms of decreased ATP concentrations in the cells, leading to marked decrease in pyruvate carboxylation in the mitochondria and depression of fatty acid synthesis in the cytoplasm.
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PMID:The effect of 2,4-dinitrophenol on adipose-tissue metabolism. 438 39

In order to study the quantitative relationship between fatty acid synthesis and pentose phosphate-cycle activity under different hormonal and dietary conditions affecting the extent of glucose uptake, cells isolated from rat epididymal adipose tissue were incubated in bicarbonate buffer containing [U-(14)C]-, [1-(14)C]- or [6-(14)C]-glucose. From the amount of glucose taken up, the production of lactate and pyruvate, and the incorporation of (14)C from differently labelled [(14)C]glucose into CO(2), fatty acids and glyceride glycerol, the rates of glucose metabolism via different pathways and the extent of lipogenesis under various experimental conditions were determined. The contribution of the pentose phosphate-cycle to glucose metabolism under normal conditions was calculated to be 8%. Starvation and re-feeding, and the presence of insulin, caused an enhancement of glucose uptake, pentose phosphate-cycle activity and fatty acid synthesis. Plots of both pentose phosphate-cycle activity and fatty acid synthesis versus glucose uptake revealed that the extent of glucose uptake, over a wide range, determines the rates of fatty acid synthesis and glucose metabolism via the pentose phosphate cycle. A balance of formation and production of nicotinamide nucleotides in the cytoplasm was established. The total amount of cytoplasmic NADH and NADPH formed was only in slight excess over the hydrogen equivalents required for the synthesis of fatty acids, glyceride glycerol and lactate. Except in cells from starved animals, the pentose phosphate cycle was found to provide only about 60% of the NADPH required for fatty acid synthesis. The results are discussed with respect to an overall control of the different metabolic and biosynthetic reactions in the fat-cells by the amount of glucose transported into the cell.
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PMID:Interrelationship and control of glucose metabolism and lipogenesis in isolated fat-cells. Effect of the amount of glucose uptake on the rates of the pentose phosphate cycle and of fatty acid synthesis. 440 62

Effects of divalent cations on the regulation of glucose transport and cAMP phosphodiesterase in isolated rat epididymal adipocytes were studied. EDTA (5 mM) moderately inhibited the binding of insulin to adipocytes in Krebs-Henseleit Hepes buffer. In the same buffer, A-23187 (an ionophore specific for divalent cations; 50 microM) plus EDTA (5 mM) almost completely blocked the insulin- or hydrogen peroxide-dependent stimulation of phosphodiesterase. This inhibition was not secondary to the loss of ATP. When cells that had been treated with A-23187 plus EDTA were washed and then exposed to 1-10 mM of divalent cations, the cellular phosphodiesterase activity was elevated. Mn2+ was most stimulatory, Mg2+ was next, and Ca2+ was least effective. The stimulatory effects were enhanced by insulin. In the presence of insulin, Mn2+ at 10 mM was less stimulatory than that at 1 mM. In regular Krebs-Henseleit Hepes buffer, Mn2+ greatly stimulated phosphodiesterase if cells were first exposed to A-23187. The Mn2+-dependent stimulation was blocked by treatment of cells with 2,4-dinitrophenol. Results essentially parallel to those described above were also obtained when the rate of glucose transport was determined. The above results indicate that divalent cations mildly support the extracellular binding of insulin to its receptor, facilitate the physiological actions of insulin, and mimic the hormone actions, presumably by stimulating an intracellular enzyme.
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PMID:Effects of divalent cations on the regulation of insulin-sensitive glucose transport and cAMP phosphodiesterase in adipocytes. Insulin-like effects of divalent cations. 608 37

Since insulin is known to stimulate intracellular hydrogen peroxide production in rat epididymal fat cells, the effects of exogenous hydrogen peroxide on rates of basal and hormone-stimulated lipolysis were investigated in a perifusion system. H2O2 (60 microM) caused a weak and transient stimulation of basal lipolysis that did not interfere with subsequent activation of lipolysis by hormones. More importantly, lipolysis stimulated submaximally with ritodrine (10(-7) M) or glucagon (10(-9) M) was inhibited by H2O2 in a manner similar to insulin, although slight differences in time course were noted. Ritodrine served as a beta-adrenergic agonist resistant to oxidative destruction by H2O2. The inhibition of lipolysis was reversible upon cessation of perifusion with H2O2. These findings ruled out oxidative destruction of the hormone or cell death as explanations for the antilipolytic effect of H2O2. Like insulin, H2O2 also inhibited 1-methyl-3-isobutylxanthine (4 X 10(-6) M)-stimulated lipolysis, but whereas insulin inhibited lipolysis stimulated by dibutyryl-cAMP (4 X 10(-4) M), H2O2 further enhanced it. These findings add another case to the growing list of insulin effects on adipocytes that can be mimicked by exogenous H2O2, and they hint at a site where the mechanisms of action of the two agents may differ.
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PMID:Effects of hydrogen peroxide on basal and hormone-stimulated lipolysis in perifused rat fat cells in relation to the mechanism of action of insulin. 615 57

Pieces of rat epididymal fat tissue were maintained in a biochemically defined medium for 20 to 44 hours in either the absence or presence of a sulfonylurea at levels known to be effective in humans. Prolonged exposure of adipocytes to sulfonylureas did not influence the number of insulin receptors or their affinity to insulin or the ability of insulin to induce receptor loss (down-regulation). Also, the sulfonylureas did not influence the basal uptake of the D-glucose analogs 2-deoxyglucose and 3-O-methylglucose. However, exposure to these drugs resulted in a potentiation of the stimulatory effects of insulin on hexose transport at submaximal and maximally effective concentrations of insulin. The average potentiation was approximately 30%. In addition, sulfonylureas enhanced stimulation of hexose uptake by the insulin mimickers, hydrogen peroxide and vitamin K5. These oxidants are known to manifest insulin-like actions subsequent to insulin binding. Under conditions in which glucose transport was rate limiting, the conversion of glucose to carbon dioxide and the total lipids mirrored the findings of hexose uptake. However, at a glucose concentration of 50 mM, at which hexose transport is no longer rate limiting, sulfonylureas did not potentiate metabolism in th absence or presence of insulin. These results may help to explain the hypoglycemic action of the drug in view of the recent finding that a postreceptor deficit is present in noninsulin-dependent diabetes mellitus.
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PMID:Extrapancreatic effects of sulfonylureas. Potentiation of insulin action through post-binding mechanisms. 640 22

Tricyclic antidepressants appeared to be without effect, except for desipramine which significantly decreased whiplash motility after spermatozoa were added to eggs, and clomipramine which decreased motility and whiplash motility in epididymal sperm suspensions after pretreatment of males. Mianserin and viloxazine were also without effect, but nomifensine significantly decreased sperm motility and whiplash motility and inhibited egg penetration almost completely. After 3 h preincubation with 0.75 mmol nomifensine hydrogen maleate/l, 2/181 and 0/256 eggs were penetrated in two separate series of experiments. Control groups in these series gave medians of 90-100% penetration by 4.5-5.5 h after spermatozoa and eggs were mixed. Maleic acid had a similar effect (1/253 eggs penetrated) whilst nomifensine hydrochloride was inactive, suggesting that the effect was due to the maleate moiety of the original nomifensine hydrogen maleate salt used.
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PMID:Effect of antidepressant drugs on the in-vitro egg-penetrating ability of golden hamster epididymal spermatozoa. 668 37

An analogue of porcine insulin which differs from the native molecule in that the tyrosine residue in Pos. A19 is replaced by phenylalanine has been synthesized. The [PheA19]A chain was synthesized by the fragment condensation and purified as tetra-S-sulfonate by ion-exchange chromatography on DEAE-cellulose at pH 3.5. Conversion of the latter into the sulfhydryl form and combination with native sulfhydryl B chain yielded the [PheA19]insulin, which was purified by ion-exchange chromatography on CM-cellulose at pH 4.0 with an linear NaCl gradient. The biological activity of this analogue was 22.6% as measured by the rat epididymal adipocytes. It was suggested that in the insulin molecule the hydroxyl function of A19-tyrosine participates in an hydrogen-bond with the carbonyl function of A1-glycine. That hydrogen bond formation is critical for the stability of the hormone-receptor complex. The low biological activity found by us supports this hypothesis. The circular dichroism data in far UV suggest that the introduction of phenylalanine leaves the molecule structure essentially undisturbed, however the change observed in near UV could be accounted for the exchange.
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PMID:(A1-phenylalanine) insulin: a new synthetic analogue. 700 Jun 56

The iodination of insulin was accomplished by a modification of the lactoperoxidase method. The use of a low concentration of hydrogen peroxide (1.5 ng/ul) followed by Sephadex gel filtration and purification on a cellulose column yielded iodoinsulin with an activity equal to that of native insulin in stimulation of glucose oxidation in rat epididymal fat cells and with high specific binding to collagenase-dissociated mouse mammary cells from pregnant and lactating mice. Other hormones tested did not displace the binding. Analysis of displacement curves and scatchard plots suggests that both the affinity and the number of sites for insulin binding differ between pregnant and lactating mammary cells.
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PMID:A method for the iodination of insulin and its binding to dissociated mouse mammary cells. 701 91

A study was made of 11-desoxyprostaglandin E1 (11-desoxy-PGE1) effect on bronchial resistance, gastric secretion, indomethacin-induced ulcer in rats and adrenalin-produced lipolysis in rat epididymal adipose tissue in vitro. The drug exerted dose-dependent bronchodilator effect in doses of 1 to 100 micrograms/kg. ED50 was 18.66 micrograms/kg. The bronchodilator effect of 11-desoxy-PGE1 was 46.5 to 50.5% of alupent activity within 60 minutes and 97.8% for a period of 60 to 90 minutes. The drug administration in the presence of bronchial spasm considerably reduces the bronchodilator effect duration (down to 5 to 15 minutes). 11-desoxy-PGE1 produces dose-dependent decrease in gastric secretion (ED50 = 4000 micrograms/kg) and hydrogen ion concentration in rat gastric juice (ED50 = 2000 micrograms/kg). The use of 1-desoxy-PGE1 in rats prior to indomethacin injection protects the gastric mucosa, diminishing erosion number. ED50 was equal to 50 micrograms/kg. The drug exerts inhibitory effect on adrenalin-induced lipolysis of the epididymal adipose tissue in vitro. The most pronounced action of 11-desoxy-PGE1 is its bronchodilator effect manifesting after the minimum dose use (1 microgram/kg).
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PMID:[Biological properties of 11-deoxyprostaglandin E1]. 707 59


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