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)

Streptozotocin treatment (125 mg/kg) in the Chinese hamster induced hyperglycaemia, hypoinsulinaemia, hyperglucagonaemia and changes in body, liver, pancreas, stomach, kidney and adipose tissue weights. The pancreatic reserves of insulin and glucagon in the diabetic animals were low, but stomach glucagon high. These animals showed high levels of phosphoenolpyruvate carboxykinase and low levels of glucokinase, hexokinase, isocitrate dehydrogenase and malic enzyme, but normal levels of pyruvate kinase in the liver. Increases in lactate dehydrogenase subunit B and isozymes 2, 3 and 4 were also observed in the liver, but not in the epididymal fat pad, of the diabetic animals. N-Acetyl-beta-D-glucosaminidase was elevated in plasma, liver and heart, but not in the kidney of the treated animals. Renal alpha-galactosidase and beta-glucosidase were depressed, whereas beta-galactosidase and alpha-glucosidase remained essentially normal. These features indicated that there were considerable differences between the biochemical disorders associated with streptozotocin-diabetes in the Chinese hamster and the published observations in the rat.
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PMID:Streptozotocin-induced diabetes in the Chinese hamster. Biochemical and endocrine disorders. 59 Jun 51

Reproductive performance was studied in transgenic males from lines expressing and transmitting four hybrid genes: mouse metallothionein-I/human growth hormone (GH) (MT/hGH), MT/hGH placental variant (MT/hGH.V), MT/bovine GH (MT/bGH) and phosphoenolpyruvate carboxykinase/bGH (PEPCK/bGH). Each male was exposed to three normal females for 1 week and to three different normal females for another week. Females were examined for vaginal plugs and necropsied on day 14 of pregnancy. Males were killed for analysis of organ weights, numbers of testicular spermatids, numbers of epididymal sperm and measurements of plasma glucose concentration. Fertility of MT/hGH and MT/hGH.V transgenic males was significantly lower than in normal males, primarily because most males failed to impregnate any females. In females that became pregnant, the numbers of corpora lutea, total fetuses and live fetuses did not differ from those in females mated to normal (nontransgenic) males. Fetal crown-rump length on day 14 of pregnancy did not differ between litters sired by normal or by transgenic males. Weights of testes and seminal vesicles were significantly greater in all four types of transgenic male, but daily sperm production per unit weight (g-1) of testis was not affected and epididymal sperm reserves were either normal or slightly higher than normal. Plasma glucose concentrations were significantly higher in PEPCK/bGH mice than in other mice. Average or individual reproductive performance of transgenic males from the various lines did not correlate with any of the parameters examined except for significantly heavier seminal vesicles in MT/hGH and MT/hGH.V males than in normal males; these transgenic males exhibited a high incidence of infertility. Since hGH and hGH.V, but not bGH, are lactogenic in rodents, it was concluded that chronic stimulation of GH and prolactin receptors by ectopically produced human GHs in transgenic mice compromises male fertility by an unknown mechanism. Reduced fertility of transgenic males with MT/hGH or MT/hGH.V hybrid genes is due to failure to inseminate or impregnate females rather than to reduced numbers of spermatozoa or gross changes in the male reproductive system.
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PMID:Effects of expression of human or bovine growth hormone genes on sperm production and male reproductive performance in four lines of transgenic mice. 162 26

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

Genetically obese normotensive rats, LA/N-corpulent (cp), were fed ad libitum diets containing either 54% sucrose or cooked corn starch for 12 weeks. Twenty-four rats were used for the study; half were corpulent (cp/cp) and half were lean (cp/+ or +/+). Fasting levels of plasma insulin, glucose, corticosterone, glucagon and growth hormone, and activities of liver and epididymal fat pad glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME), and liver and kidney glucose-6-phosphatase (G6Pase), fructose 1,6-diphosphatase (FDPase), and phosphoenolpyruvate carboxykinase (PEPCK) were measured. A significant phenotype effect was observed in insulin, corticosterone, growth hormone, and liver G6PD, ME, FDPase, and kidney PEPCK, G6Pase, FDPase, and epididymal fat pad G6PD and ME (corpulent greater than lean), and glucagon (lean greater than corpulent). Diet effect (sucrose greater than starch) was significant for plasma glucose, liver ME, and kidney G6Pase. Although not significant at the P less than 0.05 level, insulin, corticosterone, liver G6PD and FDPase and kidney FDPase tended to be higher in sucrose-fed rats. This study suggests that the corpulent rat is more lipogenic and gluconeogenic than the lean, and that the hormones responsible are effective in keeping both the lipogenic and gluconeogenic enzyme activity elevated.
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PMID:Hormonal and lipogenic and gluconeogenic enzymatic responses in LA/N-corpulent rats. 399 2

Fat-cells were prepared from rat and guinea-pig epididymal adipose tissue and compared on the basis of the intracellular distributions and activities of enzymes and with respect to their utilization of various U-(14)C-labelled substrates for lipogenesis. 1. Compared with the rat, guinea-pig extramitochondrial enzyme activities differed in that aconitate hydratase, alanine aminotransferase, ATP-citrate lyase, lactate dehydrogenase, NAD-malate dehydrogenase, NADP-malate dehydrogenase and phosphoenolpyruvate carboxykinase activities were appreciably lower, whereas aspartate aminotransferase, glucose 6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase and 6-phosphogluconate dehydrogenase activities were appreciably higher. Mitochondrial activities of citrate synthase, NADP-isocitrate dehydrogenase and pyruvate carboxylase were appreciably lower, whereas mitochondrial activities of aspartate aminotransferase, glutamate dehydrogenase, NAD-malate dehydrogenase and phosphoenolpyruvate carboxykinase were higher in the guinea pig compared with the rat. 2. In general guinea-pig fat-cells incorporated acetate and lactate into fatty acids more readily than rat fat-cells, whereas rat fat-cells incorporated glucose and pyruvate more readily than guinea-pig fat-cells. 3. Acetate stimulated the incorporation of glucose into fatty acids in rat fat-cells, but had no appreciable effect upon this process in guinea-pig fat-cells. Acetate greatly decreased the incorporation of lactate into fatty acids in cells from both species. 4. Lactate/pyruvate ratios produced by incubation of guinea-pig cells with glucose+insulin were very low compared with those found with rat cells under the same conditions. 5. With glucose (+insulin) or with glucose+acetate (+insulin) as substrates guinea-pig cells produced enough NADPH by the hexose monophosphate pathway to satisfy the NADPH requirements of lipogenesis. In rat fat-cells under the same conditions, hexose monophosphate-pathway NADPH provision was not sufficient to meet the requirements of lipogenesis. 6. These results are discussed, particularly in relationship to the disposition of cytosolic reducing equivalents in the cells.
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PMID:Lipogenesis in rat and guinea-pig isolated epididymal fat-cells. 415 67

Fatty acid synthesis in adipose tissue normally proceeds at a high rate when fasted animals are refed a diet containing carbohydrate, protein, and low levels of fat. This study investigated the effect of omitting protein from the refeeding diet. Rats were fasted for 48 hr and refed either a protein-free diet or a balanced diet, and the rate of fatty acid synthesis from glucose, pyruvate, lactate, and aspartate was measured. Refeeding the animals a diet devoid of protein resulted in a low rate of fatty acid synthesis from each of these substrates as well as a reduction in carbon flow over the citrate cleavage pathway. The activities of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, NADP-malate dehydrogenase, and ATP-citrate lyase were also reduced in epididymal fat pads from these rats. On the other hand, adipose tissue phosphoenolpyruvate carboxykinase activity was five times as great as that in tissue from animals refed a balanced diet. This difference could be eliminated if actinomycin D was injected coincident with refeeding. Refeeding rats diets high in carbohydrate is not, therefore, capable of inducing high rates of fatty acid synthesis in adipose tissue in the absence of dietary proteins. Thus, liver and adipose tissue respond differently to dietary protein.
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PMID:Dietary protein and the control of fatty acid synthesis in rat adipose tissue. 534 26

ob gene regulation is as yet unknown. We first examined whether the ob gene is under physiological control by the nutritional state. Fasting produced a sharp (95%) decrease of ob mRNA in epididymal and inguinal fat pads from 24 h onward. Refeeding rapidly (3-6 h) re-induced ob gene expression and corrected it within 24 h. Similar changes in fatty acid synthase (FAS) and GLUT4 mRNAs were observed, whereas phosphoenolpyruvate carboxykinase (PEPCK) mRNA showed an opposite evolution. We next examined the potential role of insulin. In adipose tissue of streptozotocin-diabetic rats, ob mRNA levels were decreased by 80%. Insulin treatment (4 days) only marginally increased ob mRNA, but restored euglycemia and overcorrected FAS, GLUT4 and PEPCK expression. In conclusion, we provide evidence for a physiological regulation of ob gene by variations in the nutritional state. We also show that ob expression is impaired in streptozotocin-diabetic rats and only slightly restored by insulin treatment, which suggests that ob gene is not or only minimally regulated by the hormone.
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PMID:Diet- and diabetes-induced changes of ob gene expression in rat adipose tissue. 755 21

Glyceroneogenesis was assessed in epididymal adipose tissue from rats adapted to a high protein, carbohydrate-free (HP) diet. All experiments were performed in the fed state. Adaptation to the HP diet induced a two-fold increase in the activity of adipose tissue phosphoenolpyruvate carboxykinase (PEPCK). In the absence of glucose, the conversion of 14C-pyruvate (0.2, 1.0 or 5.0 mM) to glyceride-glycerol was significantly higher in adipose tissue from HP-fed rats than in controls. In the presence of glucose, rates of glycerol synthesis in tissues from HP-fed rats did not differ significantly from those in controls. Incorporation of 14C-pyruvate into fatty acids, both in the presence and absence of glucose, was not affected by the diet. The conversion of 14C-glucose (5 mM) into either glyceride-glycerol or fatty acids did not differ in HP-fed and control rats at any of the concentrations of pyruvate utilized. The data provide further evidence for the adaptative nature of adipose tissue PEPCK and suggest that in situations of reduced availability of glucose in the diet, glyceroneogenesis may be important to maintain an adequate supply of alpha-glycerophosphate for esterification of diet-derived fatty acids.
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PMID:Increased adipose tissue glyceroneogenesis in rats adapted to a high protein, carbohydrate-free diet. 759 Jun 12

The of this study was to evaluate the chronic effects of a high (waxy corn) vs. a low (mung beans) glycemic index starch diet on the lipogenic enzymes, fatty acid synthase (FAS) and lipoprotein lipase (LPL). Normal and diabetic (streptozotocin-injected on d 2 of life) male Sprague-Dawley rats consumed a diet containing 575 g/kg carbohydrates either as waxy cornstarch (WCS) or as mung bean starch (MBS). After 3 wk, neither body weights nor relative epididymal fat pad weights differed. In diabetic rats, the WCS diet induced high basal plasma insulin levels. Plasma triglycerides were not significantly affected by diet in either normal or diabetic rats. Adipose tissue and liver LPL activities were not modified by the type of starch in the diet. In normal rats, FAS activity and gene expression in epididymal adipose tissue but not in liver were greater in rats consuming the WCS diet than in those consuming MBS. To evaluate the implication of insulin in this regulation, two genes regulated by insulin [GLUT4 and phosphoenolpyruvate carboxykinase (PEPCK)] were also studied. The high glycemic index WCS diet compared with the low glycemic index MBS diet resulted in lower hepatic PEPCK mRNA in both normal and diabetic rats. Normal, but not diabetic rats fed WCS had greater GLUT4 gene expression in adipocytes than did those fed MBS. We conclude that the total replacement of 575 g/kg low glycemic index starch by a high glycemic index starch for 3 wk caused the following in normal rats: 1) high FAS activity and mRNA in adipose tissue but not in liver and 2) high GLUT4 gene expression in adipose tissue. In both normal and diabetic rats this same diet resulted in lower hepatic PEPCK mRNA. Therefore, high glycemic index starch diet is implicated in stimulating FAS activity and lipogenesis and might have undesirable long-term metabolic effects.
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PMID:A high glycemic index starch diet affects lipid storage-related enzymes in normal and to a lesser extent in diabetic rats. 980 37

Regulation of the turnover of triglycerides in adipose tissue requires the continuous provision of 3-glycerophosphate, which may be supplied by the metabolism of glucose or by glyceroneogenesis, the de novo synthesis of 3-glycerophosphate from sources other than hexoses or glycerol. The importance of glyceroneogenesis in adipose tissue was assessed in mice by specifically eliminating the expression of the cytosolic form of phosphoenolpyruvate carboxykinase (PEPCK-C), an enzyme that plays a pivotal role in the pathway. To accomplish this, we mutated the binding site for the peroxisome proliferator-activated receptor gamma (PPAR gamma) called the peroxisome proliferator-activated receptor element (PPARE), in the 5' flanking region of the PEPCK-C gene in the mouse by homologous recombination. The mutation abolished expression of the gene in white adipose tissue and considerably reduced its expression in brown adipose tissue, whereas the level of PEPCK-C mRNA in liver and kidney remained normal. Epididymal white adipose tissue from these mice had a reduced triglyceride deposition, with 25% of the animals displaying lipodystrophy. There was also a greatly reduced level of lipid accumulation in brown adipose tissue. A strong correlation between the hepatic content of triglycerides and the size of the epididymal fat pad in PPARE(-/-) mice suggests that hepatic triglyceride synthesis predominantly utilizes free fatty acids derived from the adipose tissue. Unlike other models, PPARE(-/-) mice with lipodystrophy did not exhibit the lipodystrophy-associated features of diabetes and displayed only moderate hyperglycemia. These studies establish the importance of the PPARE site for PEPCK-C gene expression in adipose tissue and the role of PEPCK-C in the regulation of glyceroneogenesis, a pathway critical for maintaining the deposition of triglycerides in adipose tissue.
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PMID:A mutation in the peroxisome proliferator-activated receptor gamma-binding site in the gene for the cytosolic form of phosphoenolpyruvate carboxykinase reduces adipose tissue size and fat content in mice. 1179 50


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