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)

The growth of gastrointestinal mucosa can be related to ingestion and digestion of diet, with fasting producing mucosal hypoplasia and hyperphagia producing mucosal hyperplasia. Experiments were designed to determine whether induction of polyamine metabolism following ingestion of a meal was related to mucosal growth. Activity of the enzyme ornithine decarboxylase (ODC) in both jejunum and ileum but not in duodenum was dependent on the presence of food in the gut; ODC activity was more than 200-fold greater in mucosa of fed rats than in fasted rats. Inhibition of ODC with difluoromethylornithine lead to mucosal atrophy in ileum but not in duodenum. Refeeding of fasted rats resulted in significant induction of ODC in duodenal, ileal, and colonic, but not fundic, mucosa. In addition, two hormones, epidermal growth factor and glucagon, were effective inducers of ileal ODC activity. Direct evidence for hormonal involvement in the postprandial rise in mucosal ODC activity was provided by experiments in rats that had undergone ileal bypass surgery. After refeeding of fasted rats mucosal ODC activity was induced in both ileum left in continuity and in the bypassed segment. Refeeding of elemental diets demonstrated that ingestion of carbohydrate alone was sufficient for maximal enzyme induction. Mixed amino acids or glyceryl trioleate were no more effective inducers than nonnutritive solutions of cellulose or saccharin. These data demonstrate that hormones which are released during ingestion and digestion of a meal are the stimuli for induction of mucosal polyamine metabolism, suggesting that food-induced mucosal growth is hormonally mediated.
 ...
PMID:Hormonal regulation of postprandial induction of gastrointestinal ornithine decarboxylase activity. 309 78

The identification of a novel protein from Drosophila melanogaster that binds both mammalian epidermal growth factor (EGF) and insulin has been reported (Thompson, K. L., S. J. Decker, and M. R. Rosner, 1985, Proc. Natl. Acad. Sci. USA., 82:8443-8447). This 100-kD protein (designated dp100) is also recognized by an antiserum against the human EGF receptor. To further characterize the properties of this protein, we have determined the binding spectrum, glycosylation state, and cellular distribution of dp100. Our results indicate that dp100 binds to other insulin-like and EGF-like growth factors with dissociation constants ranging from 10(-6) to 10(-9) M, and these ligands compete with each other for binding to dp100. All other ligands tested, including platelet-derived growth factor, transforming growth factor-beta, nerve growth factor, and glucagon, either did not bind or bound with a Kd greater than 10(-6) M. Unlike the Drosophila insulin receptor, dp100 does not bind to wheat germ agglutinin and is present in a cytoplasmic as well as a membrane-bound form that cannot be differentiated by two-dimensional PAGE. Further, dp100 is the sole transforming growth factor-alpha-binding protein detected by affinity labeling in Drosophila Kc cells. These results indicate that dp100 shares properties in common with, but distinct from, the Drosophila homologues of the insulin and EGF receptors.
 ...
PMID:Characterization of a Drosophila protein that binds both epidermal growth factor and insulin-related growth factors. 311 66

Although early work implicated PRL as the pituitary factor inducing rat hepatic PRL receptors, recent studies indicated that GH, not PRL, was responsible. The roles for these two hormones were evaluated on rat hepatocytes cultured in serum-free medium supplemented with insulin (1 microgram/ml), epidermal growth factor EGF (25 ng/ml), glucagon (500 ng/ml), cholera toxin (2 ng/ml), hydrocortisone (10(-8) M), and transferrin (1 microgram/ml) and changed daily. Ovine (o) PRL, bovine (b) GH, or human (h) GH were introduced after 2-4 days of culture, and PRL receptors were measured by determining [125I]hGH binding in the presence and absence of excess oPRL in a total particulate fraction pretreated with 3 M MgCl2. The specific binding of hGH (% per 100 micrograms protein) decreased by 8- to 10-fold (female, 17.9 +/- 0.2% to 1.5%; male, 7.0 +/- 0.1% to 0.7%) after 3 days in culture. When added after 3 days, hGH induced PRL receptors in both female and male cells with the effect being more gradual in the latter. Induction occurred with 10 ng/ml hGH and was maximal [11- to 13-fold control] at 250-1000 ng/ml. bGH and oPRL also induced PRL receptors with maximal levels attained at 250-500 ng/ml oPRL (3- to 4-fold control). The combined addition of oPRL (300 ng/ml) and bGH (300 ng/ml) yielded levels of induction comparable to that seen with hGH. Although hormone treatment restored PRL receptor levels to those seen in male rats, the much higher levels of female rats were not attained. Treatment of hepatocytes with hGH, bGH, or oPRL affected neither cell number (through 10 days of culture) nor PRL receptor affinity. At supramaximal doses hGH, PRL, and bGH down-regulated PRL receptors, but this was particularly noticeable for oPRL and hGH. 17 beta-Estradiol and testosterone added to male and female hepatocytes simultaneously with hGH had little or no effect on receptor induction. We conclude that hepatic PRL receptors are induced by both PRL and GH, each acting through its own receptor. The failure to restore receptor levels to those seen in female rats attests to the importance of other modulators. This dual regulation of the PRL receptor explains the unusual potency of hGH which binds to both PRL and GH receptors.
 ...
PMID:Prolactin (PRL) receptor induction in cultured rat hepatocytes: dual regulation by PRL and growth hormone. 334 48

An assay procedure for carnitine palmitoyltransferase is described which allows rapid measurement of the overt activity of this enzyme in isolated rat hepatocytes. In a one-step procedure digitonin permeabilizes the plasma membrane and at the same time carnitine palmitoyltransferase activity is measured. The use of the present procedure shows that carnitine palmitoyltransferase activity is regulated on the short term by different types of agonists. Thus, insulin, epidermal growth factor, vasopressin and the phorbol ester PMA inhibit carnitine palmitoyltransferase activity, whereas glucagon treatment renders the enzyme more active. These changes in enzyme activity coincide with corresponding changes in the rate of fatty acid oxidation.
 ...
PMID:Short-term regulation of carnitine palmitoyltransferase activity in isolated rat hepatocytes. 334 11

We have identified a factor from adult rat spleen which stimulates the proliferation of rat hepatocytes. The activity was found in the spleen soluble matrix fraction (1,300xg supernatant of inter-cellular fraction). No activity was found in the spleen cell homogenate, in the spleen insoluble matrix fraction or rat serum. After 4 days of incubation with the spleen factor, the cell number increased 4-fold higher than that at inoculation. The growth stimulation were observed in both fetal bovine serum supplemented medium and hormonally defined medium which contains insulin, epidermal growth factor, glucagon, growth hormone and prolactin. The level of activity in the spleen soluble matrix was not affected by partial hepatectomy or trypsinization. These data indicate that the spleen factor is different from previously characterized effectors of hepatocyte proliferation. The novel factor has been named spleen derived growth factor (SDGF).
 ...
PMID:A novel growth factor in rat spleen which promotes proliferation of hepatocytes in primary culture. 339 Jan 74

A number of peptides having trophic activity on gastrointestinal mucosa and growth factors are known to induce small intestinal ornithine decarboxylase (ODC) activity. The effect of peptides on ODC and S-adenosylmethionine (SAMDC) activities (key enzymes in polyamine biosynthesis) in isolated enterocytes is unknown. Male Sprague-Dawley rats were fasted for 72 h and injected intraperitoneally with epidermal growth factor (EGF), pentagastrin, or glucagon, or intragastrically with EGF. A similar volume of water served as a control. Villus tip, midvillus, and crypt cell fractions were collected and identified. ODC and SAMDC activities were determined in these cells 4 h after peptide injection. EGF given intraperitoneally, but not intragastrically, stimulated ODC activity along the cryptvillus column. Pentagastrin and glucagon did not induce polyamine biosynthetic enzyme activity. ODC and SAMDC activities in intestinal mucosal scrapings from fasted animals also were increased 2-4 h after intraperitoneal EGF treatment. It is possible that EGF binding at the serosal surface of the crypt enterocyte and subsequent ODC induction is important in initiating the cellular proliferation that is known to occur after treatment with this peptide.
 ...
PMID:Effect of epidermal growth factor on polyamine-synthesizing enzymes in rat enterocytes. 349 4

In freshly isolated mouse hepatocytes obtained from fasted animals, we have studied the receptors for epidermal growth factor urogastrone (EGF-URO) in terms of the electrophoretic profile, ligand affinity, and numbers of EGF-URO receptors present on the cells, and also in terms of the ability of EGF-URO to stimulate gluconeogenesis, as reflected by the increased incorporation of [3-14C]pyruvate into glucose. The effects of EGF-URO were compared with those of glucagon. Ligand-binding studies revealed that the mouse hepatocytes possess an unusually high number of EGF-URO receptors (about 3 X 10(6) binding sites/cell), with a ligand dissociation constant of 4.4 nM. The binding of EGF-URO by mouse hepatocytes was more than 10-fold higher than the previously measured binding of EGF-URO by rat hepatocytes. Crosslink-labeling studies, coupled with gel electrophoretic analysis, demonstrated the presence of intact EGF-URO receptors, although some receptor processing had occurred during the isolation procedure. EGF-URO was able to stimulate the incorporation of 3-14C-labeled pyruvate into glucose; glucagon was unable to do so. In contrast, in rat hepatocytes isolated and assayed under identical conditions, glucagon (10 nM) caused a marked (250%) stimulation of the incorporation of pyruvate into glucose. Maximally, EGF-URO caused a 34% increase in the incorporation of [3-14C]pyruvate into glucose; a half-maximal effect was observed at a concentration of 2.5 nM EGF-URO. The stimulatory effect of EGF-URO was not dependent on the concentration of pyruvate, lactate, glucose, or calcium in the incubation medium. Although raising the concentration of pyruvate in the incubation medium increased the incorporation of [3-14C]pyruvate into glycogen, EGF-URO did not cause any change in the incorporation of radioactivity into glycogen. Overall, our data point to marked differences between rat and mouse liver preparations, in terms of the hormonal regulation of glucose metabolism, and our work documents a potential role for the remarkably high number of mouse hepatocyte EGF-URO receptors in terms of the modulation of gluconeogenesis in the mouse.
 ...
PMID:Epidermal growth factor (urogastrone)-stimulated gluconeogenesis in isolated mouse hepatocytes. 349 44

The Ca2+-mobilizing actions of ADP, ATP and epidermal growth factor (EGF) and their interaction with glucagon were studied in a perfused liver system incorporating a Ca2+-selective electrode. ADP (1-100 microM), ATP (1-100 microM) and EGF (10-50 nM) all induced a net efflux, followed by a net uptake of Ca2+ in the intact liver. The co-administration of glucagon (or of cyclic AMP) with these agents resulted in a synergistic potentiation of the Ca2+ uptake response in a way which resembles the synergism observed when glucagon is administered with phenylephrine, vasopressin or angiotensin [Altin & Bygrave (1986) Biochem J. 238, 653-661]. The inability of diltiazem, verapamil and nifedipine to inhibit the Ca2+-influx response suggests that the stimulation of Ca2+ influx does not occur through voltage-sensitive Ca2+ channels. By contrast, the synergistic effects of glucagon in the stimulation of Ca2+ influx are inhibited by 10 mM-neomycin, and a lowering of the extracellular pH to 6.8. Simultaneous measurements of perfusate Ca2+ and pH changes suggest that the Ca2+ influx response is not mediated by a Ca2+/H+ exchange. The inability of neomycin and low extracellular pH to inhibit the refilling of the hormone-sensitive pool of Ca2+, after the administration of Ca2+-mobilizing agents alone, provides evidence for the existence in liver of at least two Ca2+-influx pathways, or mechanisms for regulating Ca2+ influx.
 ...
PMID:The influx of Ca2+ induced by the administration of glucagon and Ca2+-mobilizing agents to the perfused rat liver could involve at least two separate pathways. 349 82

1. Lysine and alanine uptake by pig enterocytes has been measured in piglet mid intestine both during normal development and 3 days after injection of dexamethasone and epidermal growth factor (EGF) into 3-day-old animals. 2. Alanine uptake measured in the presence of sodium increased markedly during the first 4 weeks of post-natal life. Similar effects on alanine uptake could be produced through injection of dexamethasone, but not EGF, into 3-day-old piglets. Alanine uptake measured in the absence of sodium and lysine uptake measured in the presence of sodium remained unchanged during development and unaffected by injection of dexamethasone or EGF. 3. Enterocytes capable of transporting alanine in the presence of sodium were found, by quantitative autoradiography, to cover the top 400 micron of the villus in 6-day-old and 3-4-week-old control pigs. Alanine concentrations in villus tip enterocytes in 3-4-week-old pigs were four times those found in 6-day-old animals. Qualitative examination of selected villi, however, showed alanine uptake taking place over a considerably greater area of villus surface in 6-day-old compared with 3-4-week-old animals. 4. Injection of dexamethasone and EGF into 3-day-old piglets caused an increase in crypt depth without apparent change in crypt cell proliferation. The rate at which enterocytes migrated out of the crypt and the length of individual villi also remained unchanged by dexamethasone or EGF injection. 5. Dexamethasone produces its effect on alanine uptake by acting on older enterocytes present on the upper part of the villus. These enterocytes can be shown, by calculations based on enterocyte migration rate, to have already been present on the villus at the time the pig was born. 6. The above findings are discussed in relation to the ability of villus as well as crypt enterocytes to change their programme of differentiation in response to external stimuli. The particular ability of dexamethasone to induce system A type carrier function is further discussed in relation to normal changes found to occur during neonatal development. It is finally suggested, as a working hypothesis, that endogenous glucagon might act as the final mediator of both developmentally controlled and dexamethasone-induced changes in amino acid transport.
 ...
PMID:Dexamethasone selectively increases sodium-dependent alanine transport across neonatal piglet intestine. 350 67

To determine which hormones might regulate somatomedin secretion in the fetus, we measured somatomedin levels in conditioned medium from primary cultures of fetal rat hepatocytes. We employed a bioassay [( 3H]thymidine incorporation into DNA of chick embryo fibroblasts), a displacement assay [competition for binding of radiolabeled multiplication-stimulating activity (rat insulin-like growth factor II) to the somatomedin-binding protein] for total somatomedin, and the RIA for somatomedin-C. Epidermal growth factor and dexamethasone were the most active hormones tested; total somatomedin levels were 2-3 times above control levels. Rat GH was much less stimulatory. Human placental lactogen, glucagon, and insulin had little or no effect. Stimulation of somatomedin secretion by both epidermal growth factor and dexamethasone was time and dose dependent. The maximal response occurred at 48 h at a concentration of about 1 X 10(-7) M of either hormone. In the bioassay, stimulation by epidermal growth factor, but not dexamethasone, was detected. The steroid enhanced the secretion of an inhibitor that completely masked the mitogenic activity of the increased somatomedin levels. The somatomedin secreted by fetal hepatocytes exhibited immunological cross-reactivity with human somatomedin-C, but the levels were 500-fold less than those measured by our displacement assay. This suggests that the predominant fetal rat somatomedin is not somatomedin-C. We conclude that epidermal growth factor and dexamethasone, but not GH or placental lactogen, stimulated the secretion by fetal hepatocytes of a somatomedin which resembled multiplication-stimulating activity.
 ...
PMID:Hormonal regulation of somatomedin secretion by fetal rat hepatocytes in primary culture. 387 Oct 85


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