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

Tritiated N-hydroxysuccinimide acetate was prepared with specific activities up to 5 Ci/mmole and utilized to prepare tritiated triacetyl insulin. Binding of triacetyl insulin to liver plasma membranes was measured by its capacity to displace 125I-monoiodoinsulin. At low concentrations, less than 10 ng/ml triacetyl insulin appears to be as effective as native insulin in reducing the binding of 125I-monoiodoinsulin to plasma membranes. At concentrations of 20 ng/ml and higher, triacetyl insulin is significantly less effective than native insulin in displacing binding of 125I-monoiodoinsulin to plasma membranes. The properties of triacetyl insulin in this system are not ascribable to deacetylation and conversion of the substituted product to native insulin. Biologic activity of triacetylated insulin was studied in two other in vitro systmes. A comparison was made of the capacity of native beef insulin and its triacetyl derivative to stimulate glucose oxidation by epididymal fat pads. At all three concentrations tested (2, 6, and 18 ng/ml), triacetyl insulin exerted considerable activity, although its potency was significantly less than that of native insulin. Similar effects were observed when biologic activity was measured by induction of tyrosine-alpha-ketoglutarate transaminase in a cultured liver cell system where significant activity of triacetyl insulin was found at concentrations of 10(-9)-10(-7) M. In all systems tested, the activity of triacetylated insulin could not be accounted for by deacetylation and conversion to native insulin. In all systems studied, triacetyl insulin was more resistant to degradation than was monoiodoinsulin.
 ...
PMID:Triacetylated insulin: biologic activity and resistance to degradation. 1 May 4

Intact rat epididymal fat-cells were incubated with 32Pi and the intracellular proteins separated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. One of the phosphorylated proteins has the same RF value as [14C]biotin-labelled acetyl-CoA carboxylase purified from fat-cells and is specifically precipitated after incubation with antiserum raised against acetyl-CoA carboxylase. No significant changes in the extent of phosphorylation of acetyl-CoA carboxylase were detected after exposure of the cells to insulin.
 ...
PMID:Demonstration of the phosphorylation of acetyl-coenzyme A carboxylase within intact rat epididymal fat-cells. 2 37

The relationship between the hyperinsulinaemia of obese--hyperglycaemic (ob/ob) mice and their high activity of stearic acid delta 9-desaturase compared with lean mice has been investigated. The concentrations of plasma insulin in obese mice were decreased by 71, 88 and 96% after treatment either with alloxan or food restriction to maintain the same weight as lean mice, or treatment of the weight restricted mice with alloxan followed by feeding ad libitum. The concentration of plasma insulin produced by the latter treatment was the same as in normal lean mice. After treatment the hepatic desaturase activities were 24, 68 and 19% less respectively on a cell basis than in livers from untreated obese mice, and the total epididymal fat-pad activities were lower by 16, 62 and 57%. These results suggest that hyperinsulinaemia is not essential for the increased hepatic desaturase, controlling the hepatic desaturase activity, but even this may be subject to overriding regulation by the concentration of esterified linoleic acid in the liver lipids, which was negatively correlated (r = 0.91, P less than 0.001) with desaturase activity.
 ...
PMID:The role of insulin in the regulation of stearic acid desaturase activity in liver and adipose tissue from obese--hyperglycaemic (ob/ob) and lean mice. 3 51

When isolated rat epididymal fat cells were incubated with [125I]iodoinsulin for 5 min at 37 degrees, radioactivity accumulated in the plasma membrane fraction (Peak 1) and an unidentified particulate fraction (Peak 2) as reported previously (Kono, T., Robinson, F.W., and Sarver, J.A. (1975) J. Biol. Chem. 250, 7826-7835). This accumulation of radioactivity in Peak 2 (but not that in Peak 1) was greatly impaired when cells were incubated with iodoinsulin in the presence of a variety of metabolic inhibitors that reduce the cellular content of ATP. The reduction in the ATP level coincided with a disappearance of the stimulatory effects of insulin on sugar transport and the hormone-sensitive phosphodiesterase. In contrast, ATP depletion had no significant effects, at least during a 5-to 15-min incubation, on the intracellular water space and on the basal sugar transport and phosphodiesterase activities. When cells once depleted on ATP by treatment with 2,4-dinitrophenol (1 mM; 10 min) were washed and suspended in fresh buffer, the ATP level was recovered almost fully in 10 min. This recovery coincided with the restoration of responsiveness to insulin. When cells were incubated with [125I]iodoinsulin or insulin for 5 min at 15 degrees instead of 37 degrees, a negligible quantity of radioactivity accumulated in Peak 2 and insulin failed to activate sugar transport. In contrast, under the same conditions, radioactivity accumulated in Peak 1 and insulin stimulated phosphodiesterase considerably. These results suggest that ATP, or some other compound metabolically related to ATP, may be necessary for the actions of insulin on sugar transport and phosphodiesterase. ATP, or some other related compound, may also be necessary in the formation of the radioactive Peak 2, although the physiological function and cellular location of this peak are yet to be ascertained.
 ...
PMID:Actions of insulin in fat cells. Effects of low temperature, uncouplers of oxidative phosphorylation, and respiratory inhibitors. 6 33

Male rats were made diabetic by intravenous administration of 75 mg/kg of streptozotocin and were fed, via a pair-feeding regimen, high-fat diets +/- 1,3-butanediol (BD) at 13.5 and 27% of the dietary calories for 30 days and 31 days, respectively. 1,3-Butanediol was added to the diets primarily as a replacement for fat. Food consumption and rat weight were recorded daily. Whole blood glucose concentrations were determined weekly. At sacrifice, liver, pancreas and epididymal fat pads were excised and blood samples were collected. Liver was analyzed for protein and lipid; pancreas was weighed and analyzed for insulin; fat pads were weighed and discarded; and blood was analyzed for glucose and lipid. The 13.5% BD diet increased the beta-hydroxybutyrate, acetoacetate and cholesterol concentrations, decreased the glucose concentration in blood, and increased the insulin content of the pancreas. The BD diets did not affect the concentrations of phospholipid, triglyceride, cholesterol and fatty acid in the liver; fatty acid concentrations in the blood; or the epididymal fat pad weight. The results suggest that BD produced a slight amelioration of the diabetic condition, which may have resulted from an increased capacity of the pancreas to synthesize insulin. In addition, the data provide further evidence suggesting that in the rat BD is oxidized to the ketone bodies, beta-hydroxybutyrate and acetoacetate.
 ...
PMID:Influence of 1,3-butanediol on blood glucose concentration and pancreatic insulin content of streptozotocin-diabetic rats. 12 71

Adipose tissue and liver from vitamin B6-deficient rats have an increased lipogenic capacity. Whether this phenomenon is accompanied by changes in the activities of certain enzymes involved in the metabolism of carbohydrate and lipid, or by altered transport of glucose into adipocytes, has been studied. Five glycolytic enzymes (hexokinase, phosphoglucose isomerase, phosphofructokinase, aldolase, and pyruvate kinase), two pentose phosphate pathway enzymes (glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), malic enzyme, and ATP citrate lyase were measured in the epididymal adipose tissue, livers and kidneys of vitamin B6-deficient and control rats. Vitamin B6 deficiency did not significantly affect the glycolytic enzyme levels in the tissues studied, or the dehydrogenases measured in adipose tissue and kidneys. Liver glucose-6-phosphate dehydrogenase, and adipose tissue and liver malic enzyme were significantly lowered in deficient rats compared to ad libitum and pair-fed controls. Adipose tissue and liver ATP citrate lyase activities were also significantly decreased by vitamin B6 deficiency. In the presence of insulin, the uptake of glucose and 3-O-methyl glucose, a non-metabolizable sugar, by fat pads from deficient rats was greater than uptake by fat pads from control rats. These observations suggest that the increased glucose utilization by adipose tissue and liver of vitamin B6-deficient rats is not directly related to changes in the enzymes studied, but in the case of adipose tissue, may be explained, at least in part, by enhanced glucose uptake.
 ...
PMID:Effects of vitamin B6 deficiency on liver, kidney, and adipose tissue enzymes associated with carbohydrate and lipid metabolism, and on glucose uptake by rat epididymal adipose tissue. 13 63

In the anesthetized dog normal or pretreated with phenformin (20 mg/kg per os) for 7 days, a subcutaneous injection of this biguanide (20 mg/kg) triggers a considerable hyperinsulinemia without concomitant hypoglycemia. The insulin secreted by these animals is biologically active on rat epididymal fat pads. On the other hand, epididymal fat pads of rats pretreated with phenformin display a lower response to insulin than that of non treated rats. The hypoglycemic effect of the same dose of insulin is less important in the normal dog after chronic pretreatment with phenformin.
 ...
PMID:[Lack of concordance in the effect of large doses of phenformin on insulin secretion and glycemia. Tentative analysis]. 14 95

Insulin has been shown to lower cyclic AMP (cAMP) levels in hormonally sensitive tissue. The mechanism by which this lowering occurs has not yet been fully defined. We studied the effects of insulin on rat adipose tissue cyclic nucleotide phosphodiestrase (PDE) in an incubation system. The adipose tissue used was from both normal animals and animals rendered diabetic by intravenous injections of streptozotocin. Rat epididymal fat pads were incubated in a Krebs-Ringer bicarbonate-4% albumin system with O, 100, 1,000 or 10,000 PU/ml insulin (INS); epinephrine (EPI) or glucagon (GLU) at several different concentrations. After 15 min of incubation, each tissue was homogenized, centrifugated, and the supernatant assayed for cAMP PDE activity using the breakdown of (3-H)cAMP. The data was used to characterize cAMP PDE into apparent high and low K-m PDE components. In the normal animals, INS increased Vmax of the low Km PDE components; 100 pU/ml INS, 30%, 1000 p1/ML INS, 40; and 10,000 pU/ml INS, 20%. In contrast, streptoxotocin diabetes lowered this Vmax by 30%. In the diabetic animals, INS also increased Vmax by 30%. In the diabetic animals, INS also increased Vmax of the low Km PDE component; 100 pU/ml INS, 30%; 1000 pU/ml INS, 50% and 10,000 pU/ml INS, 100%. Epinephrine at 1, 10, and 100 pg/ml stimulated low Km cAMP PDE activity by 67%, 73% and 44% respectively. The stimulatory effect of EPI on both the low and high Km cAMP PDE activity was neutralized by propranolol or adenosine. In comparison to EPI, GLU at very low concentrations, 10-9M, stimulated low Km cAMP PDE. These studies suggest that some of the biologic actions of insulin, an antilipolytic substance, are mediated through activation of low Km PDE. Furthermore, this enzymatic activity is lower in experimental diabetes. The stimulation of low Km PDE by lipolytic hormones may reflect a long-range protective action of these agents.
 ...
PMID:Effect of insulin and lipolytic hormones on cyclic AMP phosphodieterase activity in normal and diabetic rat adipose tissue. 16 58

There appear to be two classes of protein kinases in rat heart and adipose tissue, types I and II. Type I elutes from DEAE-cellulose at smaller than 0.1 M NaCl and type II at greater than 0.1 M NaCl. The type I enzyme is more readily dissociated by salt or histone than is the type II enzyme. If the type I kinase is first dissociated by cAMP, the subunits reassociate very slowly at 0 degrees C on removal of the cAMP by Sephadex G-25 chromatography, whereas those of type II reassociate very rapidly. Rat heart contains mostly type I and a small amount of type II enzyme, whereas adipose tissue contains almost exclusively the type II enzyme. The adipose tissue enzyme resembles the heart type II kinase in all of the above properties, although the two enzymes are not identical as indicated by slight differences in elution patterns from DEAE-cellulose columns. Incubation of rat epididymal adipose tissue with low concentrations of epinephrine (0.11 muM) increases glycerol production and the fraction of the protein kinase in the active form (activity ratio). The change in cAMP under these conditions is not statistically significant. The presence of insulin inhibits the epinephrine effect on glycerol production and protein kinase but has no measurable effect on cAMP levels. Incubation of adipose tissue with high epinephrine concentrations (11 muM) increases the cAMP level, the protein kinase activity ratio, and glycerol production. Under these conditions insulin decreases the cAMP level and kinase activity ratio but does not reduce glycerol production. The data suggest that very small changes in the tissue cAMP level, undetectable by the assay method, are magnified during the stepwise activation of glycerol output aided possibly by cooperative effects between cAMP and protein kinase. The procedure developed for determining the state of activation of the cAMP-dependent protein kinase in adipose tissue must be modified by reducing the salt concentration of the buffers in order to carry out similar studies in the heart. This reflects the different types of protein kinase in the two tissues. The addition of charcoal to crude extracts of heart prevents protein kinase activation by added cyclic AMP. Charcoal should therefore prevent any activation that could occur if any sequestered cAMP were released during homogenization. Charcoal addition thereby provides a means to distinguish intracellular cAMP activation of the kinase from that which might occur following cell rupture. If epinephrine-perfused hearts are homogenized in the presence of charcoal, epinephrine stimulation of the protein kinase is only slightly decreased. This indicates that the protein kinase is activated intracellularly by cAMP and suggests that all of the cAMP in the cell is available to the protein kinase; i.e., cAMP is not released during homogenization.
 ...
PMID:Hormonal regulation of adenosine 3',5'-monophosphate-dependent protein kinase. 16 70

A connecting link between carbohydrate and fat metabolism in adipose tissue is theconcentration of alpha-glycerophosphate derived predominantly from the glycolysis ofglucose entering the fat cell. However, several investigators have reported the presence of a glycerol specific kinase in the epidiymal fat-pad of the rat and obob mouse. This enzyme's presence in other mammalian adipose tissue could contribute to the alpha-glycerophosphate pool and thus affect both carbohydrate and fat metabolism within the fat cell. Glycerokinase was demonstrated in isolated fat cells obtained from the subcutaneous, perirenal, epididymal, and dorsal intrascapular brown fat depots of the adultmale rat. It was found to be particularly sensitive to in vivo lipogenic stimuli in both the subcutaneous and the brown adipose tissue and concluded that insulin is involved in adipose glycerokinase stimulation. Therefore, the main function of glycerokinase in normal adipose tissue may be to augment the anabolic action of insulin. It isfurther suggested that deviation from the normal control of this lipogenic enzyme couldlead to a gradual accumulation of fat and eventual obesity.
 ...
PMID:Glycerokinase in mammalian adipose tissue: stimulation by lipogenic substances. 16 85


1 2 3 4 5 6 7 8 9 10 Next >>