Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ATP-Mg++ (10 mumoles/100 g, iv) increased the LD50 for Salmonella enteritidis lipopolysaccharide (endotoxin) in male Holtzman rats (300 +/- 10 g) from 1.3 to 6.0 mg/rat. While endotoxin at 3 mg/rat iv 5 hr previously induced hypoglycemia to 12 +/- 4 mg/dl, ATP cotreatment blunted the hypoglycemia; i.e., plasma glucose values were 78 +/- 6 mg/dl. ATP treatment prevented the depression in gluconeogenesis induced by endotoxin as evaluated in vivo by the conversion of 14C-alanine to 14C-glucose. ATP treatment also reduced the hypercatabolism of U-14 C-glucose to 14CO2 in vivo and by epididymal fat pads in vitro. A role for ATP in preventing disruption of glucose homeostasis and development of endotoxin shock via counteracting insulin is suggested.
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PMID:Protection against endotoxin shock and impaired glucose homeostasis with ATP. 33 38

1. Evidence is presented that exposure of epididymal fat-pads from fed rats to insulin leads to a marked diminution in the Km for phosphoenolpyruvate of pyruvate kinase. Effects of insulin may be readily demonstrated in experiments both in vivo and in vitro and are not secondary to the activation by the hormone of glucose transport. No effect of insulin is apparent in tissues from 48 h-starved animals. 2. The mechanism of the effect of insulin on pyruvate kinase was not established. The observed changes in Km do not appear to be the result of alterations in the amounts of bound effectors such as fructose 1,6-bisphosphate and alanine. Rather, as the effect persists in incubated extracts, it appears that a change in the degree of phosphorylation or some other covalent modification of the enzyme may be involved.
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PMID:Acute regulation of pyruvate kinase activity in rat epididymal adipose tissue by insulin. 48 31

Insulin antagonism characterizes infection, but the mechanism is unknown. Previous studies have been performed during the acute catabolic stage of infection, and the resultant metabolic changes reflect this decreased food intake and weight loss. To delineate metabolic alterations due to infection itself, rats with pyelonephritis induced by tail-vein injection of 1 ml. of Streptococcus faecalis (10(9) bacteria per milliliter) were studied two weeks later during a period of near-normal weight gain and food intake. Fasting growth hormone concentrations (nanograms per milliliter) in the pyelonephritic rats were nearly five times normal (45.8 vs. 9.9). Intra-arterial glucose and insulin tolerance tests were impaired. Early glucose-induced insulin release was depressed. Fat pads from infected rats manifested higher basal lipolysis per cell. Glycerol-mediated gluconeogenesis by liver slices was decreased. This pathway was unaffected by insulin in infected rats but readily inhibited in control rats. The following metabolic parameters were similar in control and infected animals: (in vivo) fasting concentrations of plasma glucose, free fatty acids, triglycerides, total corticoids, creatinine, insulin, glucagon, molar ratios of insulin and glucagon, glucose and insulin responses to tolbutamide, and glucagon and free fatty acid suppression after glucose; (in vitro) glucose metabolism by muscle and fat, epinephrine- and theophylline-stimulated lipolysis and re-esterification by epididymal fat pads, fasting hepatic glycogen content, glucose production by liver slices with and without alanine. No plasma insulin antagonist was found in the infected rats. Metabolic alterations in infected rats can be demonstrated independently of the associated catabolism. Increased growth hormone secretion cannot explain all of these changes.
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PMID:Metabolic studies in the pyelonephritic rat. 117 60

This study investigated the hypothesis that dehydroepiandrosterone (DHEA) functions as an antiobesity agent by promoting energy wastage via hepatic substrate cycling in prediabetic male BHE/cdb rats. Weanling BHE/cdb rats fed a 65% glucose diet were injected intraperitoneally daily with either DHEA (0.35 mol/kg body wt) or vehicle (1 mL/kg body wt) for 7 wk. The DHEA treatment significantly (P less than 0.05) reduced body weight gain. The DHEA-treated rats had epididymal and retroperitoneal fat pads that were 40% and 66% lighter, respectively, than those of control rats. The residual carcasses (i.e., minus fat pads, liver and ingesta) of DHEA-treated rats contained a significantly lower percentage of fat than those of control rats. The DHEA treatment significantly reduced fasting serum glucose and triglycerides without affecting total or HDL cholesterol. Isolated hepatocytes from DHEA-treated rats converted 2.5 times as much [U-14C]glucose to 14CO2 and one-half as much alanine to glucose as did hepatocytes from control rats. The DHEA treatment increased the specific activities of malic enzyme and lactate dehydrogenase 4.0- and 1.8-fold, respectively. Hepatocytes from DHEA-treated rats tended (P less than 0.08) to have lower phosphoenolpyruvate carboxykinase activities than hepatocytes from control rats. These data suggest that DHEA treatment exerts some of its antiobesity and antidiabetic effects in prediabetic, lipemic BHE/cdb rats by promoting hepatic glucose oxidation and reducing gluconeogenesis.
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PMID:Antiobesity effects of dehydroepiandrosterone are mediated by futile substrate cycling in hepatocytes of BHE/cdb rats. 183 18

Concentrations of amino acids were measured in arterial and testicular venous blood, and in fluids from the seminiferous tubule, rete testis, and the caput, corpus, and cauda epididymidis. There were no significant differences in the concentrations of any amino acids between arterial and testicular venous blood, whereas there were significant differences between arterial/venous blood and testicular interstitial fluid. The predominant amino acids measured within seminiferous tubule fluid (STF) and rete testis fluid (RTF) were glycine, alanine, glutamate, and glutamine. RTF contained approximately equal concentrations of basic and total amino acids, but 17 times higher acidic amino acids and 1.2 and 1.3 times lower uncharged polar and nonpolar amino acids, respectively, compared to STF. The concentration of total amino acids within caput fluid reached over 50 nmol/L, but then declined to approximately 50% and 0.1% of caput for corpus and cauda, respectively. The predominant amino acids measured within epididymal luminal fluids were glutamate and taurine; glutamate contributed to approximately 90% of the total amino acids measured in caput fluid. The presence of glutamate and taurine within the epididymal lumen is due primarily to a direct contribution from the epididymal epithelium, as measured using the split-drop stopped-flow microperfusion technique. Several other amino acids within the lumen also originate from the epididymal epithelium. Amino acids contribute approximately 20%, 9%, and 2% of the total osmolality of caput, corpus, and cauda fluid, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The testicular and epididymal luminal amino acid microenvironment in the rat. 208 76

MTP-1307, 7,8-dihydro-2-(4-methylpiperazinyl)-4-(1-pyrrolidinyl)-6H- thiopyrano[3,2-d]pyrimidine dimaleate, is a novel oral hypoglycemic agent, structurally different from any existing hypoglycemic drugs. In fasted rats, the hypoglycemic effect of MTP-1307 was accompanied by elevation of the plasma insulin. In glucose tolerance tests, MTP-1307 suppressed the hyperglycemia after glucose loading and significantly enhanced the glucose-induced insulin secretion. In isolated hepatocytes from fasted rats, MTP-1307 inhibited gluconeogenesis from lactate and alanine. Furthermore, MTP-1307 increased the lactate/pyruvate ratio but did not increase the lactate level. MTP-1307 did not influence glycogenolysis in isolated hepatocytes from fed rats. In genetically diabetic ob/ob mice, MTP-1307 decreased the blood glucose level and improved glucose tolerance, but did not affect the level of plasma insulin. MTP-1307 increased 14CO2 production from glucose in isolated epididymal fat pads of ob/ob mice. Thus, these findings suggest that MTP-1307 produces hypoglycemic activities not only in normal animals but also in genetically diabetic animals, and that the hypoglycemic mechanism of MTP-1307 involves the promotion of glucose utilization in adipose tissue and, partially, the inhibition of gluconeogenesis in the liver and the stimulation of insulin release from the pancreas.
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PMID:Pharmacological studies on the hypoglycemic effect of 7,8-dihydro-2-(4-methylpiperazinyl)-4-(1-pyrrolidinyl)-6H-thi opyrano [3,2-d] pyrimidine dimaleate (MTP-1307), a novel hypoglycemic agent. 266 87

Changes in the chromatin structure of boar late spermatids maturing to spermatozoa were studied by chemical modification of their nuclei with dansyl (Dns) chloride. Protamine was isolated from the dansylated boar spermatid and sperm nuclei, and its dansylated sites and degrees of dansylation were determined by sequence analysis. The N-terminal Ala-1, Tyr-3 and Tyr-42 of the protamine molecule in cauda epididymal sperm nuclei were dansylated 27%, 22% and 40%, respectively, whereas the respective residues in late spermatid nuclei were about 1.5-times as reactive as those in cauda epididymal sperm nuclei. However, the dansyl ratio of Tyr-3 to Tyr-42 remained unchanged from the late spermatid to mature sperm nuclei. SDS treatment did not affect the reactivity of cauda epididymal protamine and that of Ala-1 of caput epididymal protamine, but raised that of Tyr-3 and Tyr-42 of caput epididymal protamine by a factor of about 1.5. As a result of the SDS treatment, caput epididymal protamine came to have almost the same reactivity as late spermatid protamine. These facts suggest that the fundamental structure, in terms of DNA-protamine interaction, of sperm chromatin was already formed at the stage of the late spermatid, and then during epididymal transit the sperm chromatin was more tightly condensed, with increasing disulfide cross-links, thereby acquiring insensitivity towards the SDS-treatment.
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PMID:Changes in chromatin structure of boar late spermatids to mature spermatozoa by using modification with dansyl chloride. 273 47

1. Phosphate-dependent glutaminase activity in the epididymal fat-pad was 15.1 nmol/min per mg of protein. Glutaminase activity demonstrated differences with respect to adipose-tissue sites. Considerable variation was found in different sites of adipose tissue from lean control and Zucker obese animals. 2. Adipocytes incubated in the presence of 2 mM-glutamine utilized glutamine at a rate of 1.8 mumol/h per g dry wt., and glutamate, ammonia, lactate and alanine were produced. Addition of glucose plus insulin increased the rates of glutamine utilization and glutamate, ammonia, lactate and alanine production. Isoprenaline alone or plus glucose further stimulated the rate of glutamine utilization and formation of end products. 3. The rate of incorporation of 14C from glutamine into CO2 was similar to that of glucose, but the rate of incorporation into triacylglycerol was much less. Addition of unlabelled glucose or glucose plus insulin stimulated the rate of incorporation of [14C]glutamine into triacylglycerol, but had no effect on that of 14CO2 formation. Isoprenaline plus glucose increased the rate of incorporation of [14C]glutamine into CO2, but decreased the rate of incorporation into triacylglycerol. 4. In the absence of insulin, the rate of [14C]glutamine incorporation into triacylglycerol was related to the glucose concentration (0-10 mM). However, in the presence of insulin, the rate of incorporation of [14C]glutamine was maximal at 1 mM-glucose.
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PMID:Glutamine metabolism in isolated incubated adipocytes of the rat. 289 33

Aminopeptidase A (AP-A) was analysed in the reproductive organs of the boar, bull, gerbil and man. High hydrolysis of alpha-L-glutamyl-beta-naphthylamide (GluNA) and alpha-L-aspartyl-beta-naphthylamide (AspNA) with activation by alkaline earth metals was detected in the ampulla, seminal vesicles, and seminal vesicle secretions of the bull and in the cauda epididymis of the boar and gerbil. In man, weak AP-A activity was found in all reproductive tissues. Histochemically, AP-A was localized in the epithelial cells of tissues having a high specific activity for the enzyme. AP-A was absent from human seminal fluid, whilst bovine seminal fluid had strong, and boar seminal fluid weaker, AP-A activity. Gel filtration of bull seminal vesicle secretions and seminal fluid, boar seminal fluid or an homogenate of boar and gerbil epididymal cauda and human epididymis and seminal vesicles on Sephacryl S-300 resulted in a major high-molecular-weight activity peak A at Ve/Vo = 1.17 and another low-molecular-weight peak B at Ve/Vo = 1.51 (man), 1.62 (boar, bull) or 1.75 (gerbil). This fractionation was not in all cases able to separate AP-A from aminopeptidase(s), which were active on L-alanine-beta-naphthylamide (AlaNA) but showed no activation by alkaline earth metals. Homogenates of bovine epididymis showed only the low-molecular-weight GluNA peak B, but two areas of activity for AlaNA hydrolysis. In bovine seminal vesicles and porcine epididymis, AP-A activity appeared to be linked with the functional maturity of these organs. The high-molecular-weight AP-A (peak A) appeared to be the predominant form in seminal fluid.
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PMID:Variable distribution of aminopeptidase A in male reproductive organs of mammals. 384 Apr 55

1. Monochloroacetate, dichloroacetate, trichloroacetate, difluoroacetate, 2-chloropropionate, 2,2'-dichloropropionate and 3-chloropropionate were inhibitors of pig heart pyruvate dehydrogenase kinase. Dichloroacetate was also shown to inhibit rat heart pyruvate dehydrogenase kinase. The inhibition was mainly non-competitive with respect to ATP. The concentration required for 50% inhibition was approx. 100mum for the three chloroacetates, difluoroacetate and 2-chloropropionate and 2,2'-dichloropropionate. Dichloroacetamide was not inhibitory. 2. Dichloroacetate had no significant effect on the activity of pyruvate dehydrogenase phosphate phosphatase when this was maximally activated by Ca(2+) and Mg(2+). 3. Dichloroacetate did not increase the catalytic activity of purified pig heart pyruvate dehydrogenase. 4. Dichloroacetate, difluoroacetate, 2-chloropropionate and 2,2'-dichloropropionate increased the proportion of the active (dephosphorylated) form of pyruvate dehydrogenase in rat heart mitochondria with 2-oxoglutarate and malate as respiratory substrates. Similar effects of dichloroacetate were shown with kidney and fat-cell mitochondria. Glyoxylate, monochloroacetate and dichloroacetamide were inactive. 5. Dichloroacetate increased the proportion of active pyruvate dehydrogenase in the perfused rat heart, isolated rat diaphragm and rat epididymal fat-pads. Difluoroacetate and dichloroacetamide were also active in the perfused heart, but glyoxylate, monochloroacetate and trichloroacetate were inactive. 6. Injection of dichloroacetate into rats starved overnight led within 60 min to activation of pyruvate dehydrogenase in extracts from heart, psoas muscle, adipose tissue, kidney and liver. The blood concentration of lactate fell within 15 min to reach a minimum after 60 min. The blood concentration of glucose fell after 90 min and reached a minimum after 120 min. There was no significant change in plasma glycerol concentration. 7. In epididymal fatpads dichloroacetate inhibited incorporation of (14)C from [U-(14)C]glucose, [U-(14)C]fructose and from [U-(14)C]lactate into CO(2) and glyceride fatty acid. 8. It is concluded that the inhibition of pyruvate dehydrogenase kinase by dichloroacetate may account for the activation of pyruvate dehydrogenase and pyruvate oxidation which it induces in isolated rat heart and diaphragm muscles, subject to certain assumptions as to the distribution of dichloroacetate across the plasma membrane and the mitochondrial membrane. 9. It is suggested that activation of pyruvate dehydrogenase by dichloroacetate could contribute to its hypoglycaemic effect by interruption of the Cori and alanine cycles. 10. It is suggested that the inhibitory effect of dichloroacetate on fatty acid synthesis in adipose tissue may involve an additional effect or effects of the compound.
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PMID:Mechanism of activation of pyruvate dehydrogenase by dichloroacetate and other halogenated carboxylic acids. 447 69


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