Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat hepatocytes were cultured in a modified HI-WO/BA medium for 13 days, and the combined effect of dexamethasone, 10(-7) M, insulin, 10(-8) M, and glucagon, 10(-9) M on the DNA-content, and on the activity of several enzymes, the secretion of albumin and the rate of ethanol oxidation was investigated. The effect of ethanol on these parameters was also studied. All parameters measured declined with time in the hormone-free cultures. In hormone-supplemented cultures, the DNA-content, the activity of glucokinase, pyruvate kinase, hexokinase and lactate dehydrogenase and the secretion of albumin was maintained at reasonable levels throughout the 13 days, whereas both the activity of alcohol dehydrogenase and the rate of ethanol oxidation fell significantly, although less than in hormone-free cultures. Addition of 50 mM ethanol to the hormone-supplemented culture medium caused a ca. 20% fall in the activity of glucokinase and pyruvate kinase and a 20% increase in alcohol dehydrogenase activity. No effect of ethanol was observed on the activity of hexokinase and lactate dehydrogenase or on the secretion of albumin.
 ...
PMID:Long-term culture of hepatocytes: ethanol oxidation and effect of ethanol on enzyme activities and albumin secretion. 332 6

The biliary secretion of protein in response to bile acids and other agents known to increase bile flow was examined in a chronic bile fistula dog model. Infusion of 25, 50, or 75 mumole/kg/hr sodium taurocholate after 3 hr of bile fistulization increased biliary protein output significantly by 52, 86, and 108% respectively compared to preinfusion values. A proportionate increase in biliary albumin output during taurocholate choleresis was demonstrated. Protein outputs during bile fistulization without taurocholate replacement were unchanged. The non-micelle-forming bile acid dehydrocholate markedly increased bile flow but did not change protein output. Similarly, the hormonal choleretics glucagon and secretin caused significant decreases in biliary protein concentration but no change in protein output. These data indicate a correlation between biliary protein secretion and bile acid-dependent bile flow. It is likely that regulation of certain proteins is dependent on the micelle-forming properties of bile acids.
 ...
PMID:Regulation of biliary protein secretion in dogs. 334 Jun 24

Hepatocytes are in a dynamic equilibrium with the plasma zinc supply. Kinetic analysis of zinc uptake by isolated rat liver parenchymal cells defines two intracellular pools. In one pool zinc is bound relatively weakly and equilibrates rapidly with the medium at 37 degrees C. In the other pool zinc is bound tightly and interacts with the medium slowly at 37 degrees C. Of the two intracellular pools, the slower responding component represents an exchange process with the bulk of total cell zinc. The slow phase of uptake is saturable with albumin in the medium. The smaller pool is in rapid equilibrium with the medium and represents a labile zinc pool that accounts for net zinc accumulation. Both intracellular pools respond to hormonal stimuli. The factors that augment the uptake/exchange of zinc, namely glucocorticoids, glucagon, epinephrine, and dibutyryl cyclic AMP, are also those that stimulate metallothionein gene expression in hepatocytes. Changes in zinc flux into intracellular pools are directly related to the metallothionein content of hepatocytes. Characteristics of the labile zinc pool suggest that it may serve as an initial intermediate in zinc metabolism by hepatocytes as well as more general aspects of liver function related to zinc.
 ...
PMID:Zinc uptake and metabolism by hepatocytes. 353 46

A 30% body surface area, open-flame, full-thickness burn of adult rats induced a 4-day period of anorexia that was followed by hyperphagia beginning on postburn day 10. The hyperphagic burned rats also exhibited increased resting energy expenditure and no gain in body weight, suggesting hypermetabolism. Plasma levels of immunoreactive insulin and albumin were decreased in both groups of burned rats; immunoreactive pancreatic glucagon concentrations were elevated only in the anorectic burned rats. Plasma levels of epinephrine were elevated in the hyperphagic burned rats. In the brain, dopamine metabolism appeared to be increased in the corpus striatum, nucleus accumbens, and amygdala of anorectic burned rats; norepinephrine levels were elevated in the hypothalamus and nucleus accumbens of the hyperphagic-hypermetabolic rats. These data indicate that this animal model of major burn trauma exhibits anorexia, hyperphagia, catabolism, and hypermetabolism. Furthermore, elevated dopamine metabolism appears to be associated with the anorexia, while the hyperphagia-hypermetabolism may be mediated by norepinephrine.
 ...
PMID:Burn-induced alterations in feeding, energy expenditure, and brain amine neurotransmitters in rats. 357 6

Elevated plasma levels of the so-called catabolic hormones (glucocorticoid, epinephrine, glucagon) have been observed in severely injured patients, and infusion of these hormones to normal subjects has reportedly simulated several metabolic aberrations characteristic of severe trauma and sepsis. We recently reported that amino acid uptake was reduced in soleus muscle, heart, and diaphragm, and increased in the liver, of septic rats. The purpose of the present study was to investigate organ amino acid uptake in nonseptic rats infused with catabolic hormones. Central venous catheters were placed in male Sprague-Dawley rats (100-150 g) and after 24 hr hormones (glucagon 5 micrograms/kg/hr, epinephrine 6 micrograms/kg/hr, corticosterone 4.2 mg/kg/hr) or vehicle (saline, ascorbic acid 1 mg/ml, albumin 3 mg/ml) was infused for 72 hr. Animals were housed in metabolic cages and allowed food and water ad lib. One hour prior to sacrifice, alpha-[3H]aminoisobutyric acid (AIB) (2.5 microCi), a nonmetabolized amino acid analog mainly transported by system-A, was injected intravenously. Animals were killed and organs were removed, weighed, and dissolved in tissue solubilizer for measurement of radioactivity. AIB uptake was significantly elevated in all organs of catabolic hormone-infused animals studied. The results suggest that catabolic hormones may be involved in the pathogenesis of increased amino acid uptake in the liver during sepsis. Inhibited amino acid uptake in skeletal muscle during sepsis, however, is probably not primarily mediated by catabolic hormones.
 ...
PMID:Effect of catabolic hormone infusion on organ amino acid uptake. 357 67

The developmental change in gene expression of tryptophan 2,3-dioxygenase (EC 1.13.11.11) in rat liver was studied by dot-blot hybridization with cDNA of the enzyme as a probe. The mRNA of tryptophan oxygenase is not expressed in fetal liver, but is expressed very slightly 1 day after birth. Its expression increases first gradually until 12 days after birth and then rapidly, and reaches the adult level about 22 days after birth. On the other hand, mRNA of albumin in the liver, measured with its cDNA, increases rapidly in the late fetal period and reaches almost the adult level at the time of birth. Studies on in vitro transcription by the nuclear run-off technique showed that the developmental increases in the mRNAs of tryptophan oxygenase and albumin are caused by an increase in the rates of transcription of their genes. Treatment of rats with cortisol significantly increased the amount of tryptophan oxygenase mRNA in the liver from soon after birth. This treatment did not increase mRNA of albumin. It is suggested from these findings that the gene of tryptophan oxygenase is switched on as early as the first day after birth in the few differentiated hepatocytes present in the liver and that the number of these differentiated cells gradually increases during early postnatal development. Although injected glucocorticoid stimulated transcription of the gene of tryptophan oxygenase precociously during this period, presumably in vivo the activity of tryptophan oxygenase normally increases about 2 weeks after birth, because this is when the plasma concentrations of glucocorticoid and glucagon increase sufficiently to be effective.
 ...
PMID:Developmental control of gene expression of tryptophan 2,3-dioxygenase in neonatal rat liver. 374 71

In primary cultures of adult rat hepatocytes, transcription of the albumin gene, measured as incorporation of [alpha-32P]UTP into mRNA in isolated nuclei, decreased dramatically during culture without addition of serum and hormone, becoming almost negligible 10 h after plating. Of the hormones tested, dexamethasone (0.1 microM) prevented this decrease and restored the transcription within 2 h to the same level as that before culture. The half-maximum dose of dexamethasone for induction of transcription of the albumin gene was about 30 nM. The in vitro finding that expression of the albumin gene is strictly regulated by glucocorticoid was confirmed by an in vivo experiment in adrenalectomized rats showing that the transcription decreased markedly 14 days after adrenalectomy, but was restored rapidly by administration of hydrocortisone. This finding was also supported by identification of a glucocorticoid regulatory sequence from -50 to -62 base pairs between the TATA box and CAT box upstream of the 5'-end of the albumin gene. Cycloheximide inhibited the induction of transcription of the albumin gene by dexamethasone, suggesting that a rapidly induced mediator protein, which is also regulated by glucocorticoid, is involved in the induction of albumin gene expression by glucocorticoid. The albumin gene was also regulated by various other hormones besides glucocorticoid. Glucagon markedly enhanced the transcription induced by dexamethasone, although glucagon alone had no effect. Conversely, epinephrine suppressed stimulation of expression of the albumin gene by dexamethasone. Insulin and triiodothyronine had no effect on transcription of the albumin gene. From these findings we conclude that expression of the albumin gene depends strictly on glucocorticoid, and this dependence is modulated by other hormones.
 ...
PMID:Glucocorticoid-dependent expression of the albumin gene in adult rat hepatocytes. 378 47

Studies were conducted to explore hormonal and nutritional factors that might be involved in the regulation of retinol-binding protein (RBP) synthesis and secretion by the liver. The studies employed primary cultures of hepatocytes from normal rats. When cells were cultured in Dulbecco's modified Eagle's medium alone, a high rate of RBP secretion was observed initially, which declined and became quite low by 24 hr. Supplementing the medium with amino acids maintained RBP and albumin secretion at moderate (but less than initial) rates for at least 3 days. Further addition of dexamethasone maintained the production and secretion rates of RBP, transthyretin, and albumin close to the initial rates for up to 3-5 days in culture. The effects of dexamethasone were not rapid and were not specific for RBP; half-maximal effects were seen at 10(-9) to 10(-8) M levels. Hormonally treated hepatocytes produced and secreted RBP, transthyretin, and albumin at both absolute and relative rates similar to physiological values, as estimated from rates reported by others from studies in vivo (with both rats and humans) and with perfused livers. Glucagon addition partially maintained the secretion rates of these 3 proteins, but less effectively than did dexamethasone. A number of other hormones, added singly or in combination, did not affect RBP production or secretion. Addition of retinol to the cultured normal hepatocytes was without effect upon RBP secretion. These studies show that supplementing the culture medium of hepatocytes with amino acids and dexamethasone maintains RBP production and secretion for several days. In normal hepatocytes, with ample supply of retinol available within the cell, addition of exogenous retinol does not appear to influence RBP metabolism or secretion by the cells.
 ...
PMID:Effects of nutritional and hormonal factors on the metabolism of retinol-binding protein by primary cultures of rat hepatocytes. 380 30

Incubation of rat adipocytes with the same range of noradrenaline concentrations that stimulate lipolysis caused a rapid and stable decrease in the activity of fatty acyl-CoA synthetase. Corticotropin, glucagon and dibutyryl cyclic AMP also decreased the activity of the enzyme. The effect of noradrenaline was apparent over a wide range of concentrations for the three substrates of the enzyme. A novel fluorescence assay of fatty acyl-CoA synthetase using (1,N6-etheno)-CoA is described. The effect of noradrenaline was not abolished by inclusion of albumin in homogenization buffers, persisted through subcellular fractionation and isolation of microsomes (microsomal fractions) and even survived treatment of microsomes with Triton X-100. The effect of noradrenaline was rapidly reversed within cells by the subsequent addition of insulin or propranolol. The inclusion of fluoride in homogenization buffers did not alter the observed effect of noradrenaline. Additions of cyclic AMP-dependent protein kinase to adipocyte microsomes caused considerable phosphorylation of microsomal protein by [gamma-32P]ATP, but did not affect the activity of fatty acyl-CoA synthetase.
 ...
PMID:Reversible inactivation by noradrenaline of long-chain fatty acyl-CoA synthetase in rat adipocytes. 388 97

The effect of gram-negative sepsis on the kinetics and oxidation of very low-density lipoprotein (VLDL) fatty acids was assessed in conscious dogs in the normal state and 24 h after infusion of live Escherichia coli. VLDL, labeled with [2-3H]glycerol and [1-14C]palmitic acid, was used to trace VLDL kinetics and oxidation, and [1-13C]palmitic acid bound to albumin was infused simultaneously to quantify kinetics and oxidation of free fatty acid (FFA) in plasma. Sepsis caused a fivefold increase in the rate of VLDL production (RaVLDL). In the control dogs, the direct oxidation of VLDL-fatty acids was not an important contributor to their overall energy metabolism, but in dogs with sepsis, 17% of the total rate of CO2 production could be accounted for by VLDL-fatty acid oxidation. When glucose was infused into dogs with insulin and glucagon levels clamped at basal levels (by means of infusion of somatostatin and replacement of the hormones), RaVLDL increased significantly in the control dogs, but it did not increase further in dogs with sepsis. We conclude that the increase in triglyceride concentration in fasting dogs with gram-negative sepsis is the result of an increase in VLDL production and that the fatty acids in VLDL can serve as an important source of energy in sepsis.
 ...
PMID:Effect of sepsis on VLDL kinetics: responses in basal state and during glucose infusion. 389 May 59


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