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

When adult rat hepatocytes were cultured in plastic Petri dishes in a medium containing insulin and glucagon, supplementation with epidermal growth factor (EGF) had a pronounced effect on their viability, morphology, and biochemical integrity. Transmission and scanning electron microscopic studies showed that after 1 week cells denied EGF accumulated numerous non-electron-dense bodies and filamentous whorls, had irregular nuclei, and exhibited atypical cell surfaces. In contrast, cells grown for 2-3 weeks in the presence of EGF had well-preserved cellular organelles and remained as an epithelial-like monolayer. After 3 weeks EGF-exposed cultures were still inducible for liver-specific tyrosine aminotransferase, and both rat albumin and rat transferrin were recoverable from the culture medium. Virtually no viable cells were present at 3 weeks in EGF-deprived cultures.
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PMID:Effect of epidermal growth factor on cultured adult rat hepatocytes. 614 10

Treatment of rat superior cervical ganglia in culture with nerve growth factor (NGF) increases the amount of radioactive phosphate incorporated into a nuclear protein band. This band migrates coincidentally with H1 histone on 10% sodium dodecyl sulfate/polyacrylamide gels. The increase in phosphate incorporation is at least 70% and occurs only in tissues known to be responsive to NGF. It is not produced by treatment with related peptides, but is observed after the addition of dibutyryl cyclic AMP. An increase in phosphorylation can be detected after 1 h, and can be seen with as little as 10 ng/ml of NGF in the medium. Neither actinomycin D nor cycloheximide inhibits the effect. When the nuclei are extracted with 0.2 M H2SO4 and the extract analyzed on acid-urea/polyacrylamide gels, two NGF-responsive proteins can be detected. One protein again migrates with the H1 histone marker; the other migrates more slowly than H1. These two NGF-responsive proteins have molecular weights of approximately 30,000 and are chromatin-bound. They are not soluble in 5% perchloric acid, but can be extracted from the nuclei with 0.35 M NaCl. No increase in the phosphorylation of these proteins was seen in ganglia from 6-hydroxydopamine-treated rats. The phosphorylation of the proteins in both control and NGF-treated ganglia occurs almost exclusively on serine residues. The amino acid compositions of the two nuclear proteins show that they are different from the H1 histone and different from each other. Both nerve growth factor (NGF) and epidermal growth factor (EGF) increase the incorporation of radioactive phosphate into a specific nuclear protein in cultures of PC12, a clone of rat pheochromocytoma. Purified NGF antibody blocks the effect of NGF, but not that of EGF; EGF antiserum neutralizes the effect of EGF, but not that of NGF. Insulin, glucagon, and dexamethasone are without effect. The increase in phosphorylation due to NGF can be detected within 1 h. Dibutyryl cyclic AMP increases the phosphorylation of this protein, but dibutyryl cyclic GMP does not. Neither the uptake nor the overall incorporation of [32P]orthophosphate is altered by NGF, EGF, or dibutyryl cAMP under the present experimental conditions. The nuclear protein exhibiting increased radioactivity is similar in solubility, size, and amino acid composition to one of the NGF-responsive nuclear proteins from sympathetic ganglia.
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PMID:Increased phosphorylation of specific nuclear proteins in superior cervical ganglia and PC12 cells in response to nerve growth factor. 615 55

The submandibular glands of mice and rats are not fully developed at birth. In early postnatal life, differentiation of acini takes place before that of granular convoluted tubule (GCT) cells. The latter develop from striated duct cells, and first appear in both species around 15 days of age. In mice their full development gets under way by 20 days of age and is rapid in males and slow in females, resulting in a clear sexual dimorphism in adults. In rats, GCT development is more protracted, and accelerates around 40 days of age, with no sexual dimorphism seen at any time. The course of postnatal development of several GCT cell products is correlated with the cytodifferentiation of these cells. Reliable data are available for the development of amylase, proteases (including kallikrein), renin, epidermal growth factor, and nerve growth factor. Preliminary information exists for a glucagon-like substance. Cytodifferentiation of GCT cells is under hormonal control. Androgens alone can not precociously induce GCT cells, but thyroid hormones can do so, acting either alone or synergistically with androgens.
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PMID:Postnatal developmental changes in submandibular glands of rats and mice. 616 Jan 81

Prostaglandin E1 (PGE1), a component in the hormone-supplemented, serum-free medium for the Madin Darby canine kidney (MDCK) cell line, has been proposed to increase MDCK cell growth by increasing intracellular cyclic AMP levels. The association between increased intracellular cyclic AMP and the growth stimulatory effect of PGE1 has been examined in normal MDCK cells and in PGE1-independent variants of MDCK. These variant cells have lost the PGE1 requirement for long term growth in defined medium. Normal MDCK cells had almost twofold higher intracellular cyclic AMP levels during growth in Medium K-1 (9.0 pmol/mg protein) than in Medium K-1 minus PGE1. Furthermore, PGE1-independent clone 1 had higher intracellular cyclic AMP levels in Medium K-1 minus PGE1 than normal MDCK cells in Medium K-1. This latter observation suggests that the PGE1 requirement for MDCK cell growth is associated with the low intracellular cyclic AMP levels of this cell line. An involvement of cyclic AMP in the growth response to PGE1 is supported by these observations, as well as by the growth stimulatory effects of other agents that affect cyclic AMP metabolism in MDCK cells. These agents include glucagon, isobutyl methylxanthine (IBMX), and dibutyryl cyclic AMP. The growth of PGE1-independent clone 1 was inhibited rather than stimulated by PGE1. Similarly, PGE1-independent cell growth was inhibited by IBMX and dibutyryl cyclic AMP. However, the growth response to one agent which increases cyclic AMP (glucagon) was retained in PGE1-independent clone 1. This result suggests that the effect of glucagon is not associated with increases in intracellular cyclic AMP. The growth stimulatory effect of epidermal growth factor (EGF) on normal MDCK cells was also studied. Although EGF does not act via a cyclic AMP-mediated mechanism, EGF increased normal MDCK cell growth and substituted for PGE1 in Medium K-1. Thus, EGF and PGE1 could possibly affect similar growth-related functions in MDCK cells, although by different pathways. This possibility was examined further, using PGE1-independent clone 1. EGF, like glucagon, was still growth stimulatory to the PGE1-independent cells. Consequently, the biochemical pathways by which EGF and PGE1 increase MDCK cell growth probably do not converge.
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PMID:PGE1-independent MDCK cells have elevated intracellular cyclic AMP but retain the growth stimulatory effects of glucagon and epidermal growth factor in serum-free medium. 620 19

Adult rat parenchymal hepatocytes in primary culture can be induced to enter into DNA synthesis and mitosis. The optimal conditions for hepatocyte replication are low plating density (less than 10,000 cells/sq cm) and 50% serum from two-thirds partially hepatectomized rats (48 hr after hepatectomy). Approximately 80% of the hepatocytes enter the cell cycle, and most of these cells go through mitosis. The replicating hepatocytes remain positive for glucose-6-phosphatase and negative for gamma-glutamyl transpeptidase, and they accumulate fat, in analogy to regenerating liver. Most of the replicating hepatocytes enter into multiple consecutive rounds of DNA synthesis. Dose-response studies between control animal serum and hepatocyte labeling index indicate that in unoperated animals the serum contains substances stimulatory as well as inhibitory for hepatic growth, with the inhibitory effect prevailing at high concentrations. After partial hepatectomy, the inhibitory activity disappears whereas the hepatopoietin activity reaches almost 90% of maximal biological effectiveness at 25% serum concentration. Addition of hormones to the system shows that the hepatopoietin activity is not identical to epidermal growth factor, platelet-derived growth factor, thyroxine, glucagon, or hydrocortisone. Norepinephrine abolishes the difference between control and hepatectomized serum but does not restore hepatopoietin activity when added to heat-inactivated serum. The results show that this system of replicating hepatocytes can be used to investigate the trophic factors that control growth of normal and neoplastic hepatocytes.
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PMID:Liver regeneration studies with rat hepatocytes in primary culture. 621 20

Insulin and glucagon stimulate amino acid transport in isolated rat hepatocytes. Amiloride, a specific Na+-influx inhibitor, completely inhibited the hormonal (glucagon or insulin) stimulation of alpha-aminoisobutyric acid influx by preventing the emergence of a high-affinity transport component. The drug also inhibited [14C]valine incorporation into hepatocyte protein. The half-maximal concentration of amiloride for inhibition of protein synthesis was similar to that required for inhibition of hormone-stimulated amino acid transport (approx. 0.1 mM). In primary cultured rat hepatocytes, amiloride markedly depressed the stimulation of alpha-aminoisobutyric acid transport by glucagon, or a mixture of glucagon, insulin and epidermal growth factor. These results suggest that amiloride inhibits the hormonal stimulation of hepatocyte amino acid transport by preventing the synthesis of high-affinity transport proteins. They also suggest that the hormonal stimulation of hepatocyte amino acid transport is dependent, at least partly, on Na+ influx.
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PMID:The effect of amiloride on hormonal regulation of amino acid transport in isolated and cultured adult rat hepatocytes. 626 11

Glucagon and dibutyryl cyclic AMP exerted both stimulatory and inhibitory effects on hepatocyte DNA synthesis when added to primary monolayer cultures in the presence of serum, dexamethasone, insulin and epidermal growth factor. The stimulation occurred at low concentrations of glucagon (1 pM-1 nM) or dibutyryl cyclic AMP (1 nM-1 microM), while the agents inhibited DNA synthesis at higher concentrations (usually glucagon at over 10 nM or dibutyryl cyclic AMP at over 10 microM). The stimulatory effect was stronger at low cell densities (less than 20 X 10(3) hepatocytes/cm2). When the hepatocytes were cultured at higher densities, stimulatory effects were reduced or absent and the inhibition of (hormone-induced) DNA synthesis by a high concentration of glucagon was much more pronounced than at low cell densities. These results indicate dual, bidirectional, effects of cyclic AMP on hepatocyte DNA synthesis.
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PMID:Bidirectional concentration-dependent effects of glucagon and dibutyryl cyclic AMP on DNA synthesis in cultured adult rat hepatocytes. 630 92

The binding of epidermal growth factor (EGF) and of glucagon to their receptors has been examined in single-cell suspensions obtained from livers and other organs of newborn mice homozygous for a perinatally lethal deletion that includes the albino (c) locus on chromosome 7. Competition experiments with 125I-labeled and nonradioactive EGF and Scatchard analysis of equilibrium binding data showed that hepatocytes from deletion homozygotes had only approximately equal to 20% of the number of specific EGF receptors present in cells from normal littermates. In contrast, EGF binding to single-cell suspensions from organs other than the liver was normal in deletion homozygotes. Similar results were obtained in competitive displacement experiments with 125I-labeled and nonradioactive glucagon: hepatocytes from deletion mutants showed only approximately equal to 30% of the specific glucagon binding sites found in cells from normal littermates. As in the case of EGF, the decreased binding was due to decreased numbers of glucagon receptors per cell rather than alterations in receptor affinity, and glucagon binding to single-cell suspensions from organs other than the liver was normal in the deletion mutants. The reductions in numbers of EGF and glucagon receptors are liver-cell specific as are the previously described ultrastructural and biochemical abnormalities in these mutants. The significance of cell membrane integrity and hormone-receptor interactions in the control of normal liver cell differentiation is discussed.
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PMID:Epidermal growth factor and glucagon receptors in mice homozygous for a lethal chromosomal deletion. 631 May 74

This paper summarizes recent and continuing work on circadian rhythms in the alimentary tract of rodents; these include: (1) cell proliferation, (2) activities of intestinal enzymes, and (3) behavioral aspects of spontaneous feeding and drinking. All regions of the intestinal tract show marked circadian behavior in cell proliferation. The roles of the light-dark cycle and meal timing in synchronizing such rhythms are discussed as well as the influence of epidermal growth factor, insulin, glucagon, and ACTH 1-17. Attention is called to the potential importance of these rhythms to basic research and medicine. Other circadian rhythms in the alimentary tract are reviewed briefly, such as those characterizing a host of intestinal enzymes, monosaccharide transport, and the height and width of the villi. Many of these have been shown to be cued to a feeding schedule; however, a number of the enzyme rhythms persist for one or two cycles in fasting animals, and this also is the case for the cell-proliferation rhythms. After having been acclimated to a circadian feeding schedule (within a range of 23-30 hr), rodents can on subsequent days anticipate the food an hour or more prior to its arrival. Some enzymes behave in a similar manner in that their activities increase prior to the expected intake of the daily food. These anticipatory response rhythms are under endogenous control, since both will persist in the fasted animal and both will free run when a mouse is placed under constant conditions. Somehow these animals are able to measure circadian intervals of time. This challenges the concept that the oscillations seen in enzyme activities are simply a passive consequence of feeding and fasting, respectively.
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PMID:Chronobiology of the intestinal tract of the mouse. 632 Jun 26

A single exposure to a low concentration (10(-10) mol/l) of tumor promoters [such as 12-O-tetradecanoylphorbol-13-acetate (TPA), phenobarbital and nafenopin] or hormones [such as epidermal growth factor (EGF), glucagon and insulin] or drugs [such as imidazole and indomethacin] stimulated the 24-h flow into DNA synthesis and mitosis of primary neonatal rat hepatocytes incubated in high-calcium (1.8 mmol/l) Eagle's FBS(10% v/v)-MEM. However, only tumor promoters acted as enhancers of hepatocytic DNA synthesis when a low-calcium (0.01 mmol/l) FBS-MEM was used. The activity of tumor promoters was totally suppressed by the simultaneous (or nearly such) addition of low doses (from 25.0 to 0.25 micrograms/ml; activity, from 100 to 0.7 U/ml) of exogenous bovine liver and ox and dog erythrocyte superoxide dismutase (SOD), independent of the calcium concentration of the medium. Even at the minimal dose administered, SOD effectively inhibited the stimulatory actions of TPA concentrations up to 10(-6) mol/l. SOD's blocking effect depended upon its enzymatic activity, as it was prevented by a specific inhibitor of SOD, sodium diethyldithiocarbamate (DDC). By contrast, SOD did not inhibit the growth stimulation elicited by hormones and drugs in hepatocytes maintained in high-calcium FBS-MEM. Moreover, several tumor promoters (namely TPA, phenobarbital, nafenopin, saccharin, teleocidin, benzoyl peroxide, BHT, DDT, lindane, clofibrate and melittin) stimulated DNA synthesis even when the hepatocytes were incubated in the serumless HiWoBa2000 medium, whatever its calcium concentration. In this synthetic medium, tumor promoters' stimulatory activity was again completely inhibited by the simultaneous administration of exogenous SOD. Known antioxidants such as retinoids, vitamin E, selenous acid, and 7,8-benzoflavone, when given simultaneously with TPA, also prevented the stimulation of hepatocytic growth. These results disclose the existence of two quite different mechanisms by which the growth of neonatal rat hepatocytes can be stimulated: (i) the physiological-pharmacological extracellular calcium-dependent SOD-insensitive system mediating the effects of EGF, glucagon, insulin, imidazole, and indomethacin; and (ii) the pathological extracellular calcium-independent SOD- and antioxidant-suppressible mechanism operated by agents belonging to the tumor promoters class and involving, as a critical step, the generation of superoxide anions on the surface of the hepatocyte plasmalemma.
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PMID:Exogenous Cu,Zn-superoxide dismutase suppresses the stimulation of neonatal rat hepatocytes' growth by tumor promoters. 633 36


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