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)

Sustained production of plasma proteins, notably albumin, is a reliable indicator of the differentiated state of hepatocytes. In this work, we have developed a fetal hepatocyte culture system where studying the regulation of albumin expression in proliferating liver cells. Our results show that under proliferative conditions (i.e., in the presence of EGF) fetal hepatocytes maintain albumin production above control quiescent non-treated cells. Glucagon and noradrenaline have no effect on the proliferation induced by EGF in cultured fetal hepatocytes; however, they act synergistically with the growth factor, increasing intracellular albumin levels. The maximum response is obtained by treatment of cells with EGF and noradrenaline. The stimulatory noradrenergic effect is mimicked by agents that increase cyclic AMP levels (forskolin plus IBMX). However, vasopressin or phorbol esters have no effect on albumin production, neither alone nor in combination with EGF. Dexamethasone, which does not alter the proliferative induction of EGF, increases albumin content. This effect is independent of the proliferative status of the cells and is not enhanced by glucagon, noradrenaline, or cyclic AMP increasing agents. The hormonal changes observed in albumin production partially correlate with changes in mRNA levels. This is the first time that cyclic AMP increasing agents are shown to act synergistically with EGF, increasing the expression of this liver specific gene.
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PMID:Regulation of albumin expression in fetal rat hepatocytes cultured under proliferative conditions: role of epidermal growth factor and hormones. 137

Glucocorticoid regulation of peptide hormone gene expression was studied in two cell lines derived from rodent islet cell tumors. In rat RIN1056A cells, dexamethasone reduced the levels of glucagon mRNA transcripts while markedly inducing the expression of the angiotensinogen gene. In contrast, dexamethasone had no effect on the regulation of glucagon gene expression in hamster InR1-G9 cells. Wild type InR1-G9 cells did not support the induction of the murine mammary tumor virus promoter by glucocorticoids, suggesting that these cells lacked the necessary cellular factor(s) for glucocorticoid responsiveness. Introduction of the glucocorticoid receptor into wild type InR1-G9 cells restored glucocorticoid induction of the murine mammary tumor virus promoter, but not glucocorticoid regulation of glucagon gene expression. Dexamethasone treatment of Sprague-Dawley rats had no effect on the levels of pancreatic glucagon mRNA transcripts. The results of these studies demonstrate that glucocorticoid regulation of glucagon gene expression is restricted to the immortalized RIN1056A cell line, providing additional evidence for cell-specific diversity in the regulation of peptide hormone gene expression in neuroendocrine tumors.
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PMID:Differential glucocorticoid regulation of glucagon gene expression in cell lines derived from rat and hamster islet cell tumors. 170 69

Adrenalectomized and intact rats were given constant high-dose infusions of glucagon, 0.3 mg/kg per day for 7 days, with or without low-dose dexamethasone, 0.01 mg/kg daily, to test whether glucocorticoids potentiate glucagon induction of the 5 urea cycle enzymes as they do in cultured rat hepatocytes. Glucagon did not induce any of the urea cycle enzymes in adrenalectomized Sprague-Dawley rats and only induced argininosuccinate lyase (EC 4.3.2.1) in adrenalectomized inbred Wistar-Furth rats. Dexamethasone alone induced arginase in adrenalectomized and in intact Wistar-Furth rats and restored the other enzymes to normal levels in adrenalectomized rats. In intact Wistar-Furth rats, the combination of hormones gave synergistic increases of all 5 enzymes over the responses to each hormone alone, but in adrenalectomized rats the combination was only additive or less than additive compared with the sum of single hormone responses. The lack of synergism between the two hormones in adrenalectomized rats suggest that other factors play a role in glucagon induction of this cycle.
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PMID:Dexamethasone and glucagon cause synergistic increases of urea cycle enzyme activities in livers of normal but not adrenalectomized rats. 180 64

We studied the effects of insulin, glucagon or dexamethasone on the production of apolipoprotein A-IV (apo A-IV) by cultured rat hepatocytes, using specific radioimmunoassay for rat apo A-IV. We also compared the effect of these hormones on the production of apo A-IV with those of albumin and apo A-I, reported previously. In the absence of hormones, apo A-IV and albumin in culture medium increased almost linearly for periods up to 24 h. The rates of accumulation of apo A-IV and albumin in the medium were 15.4 ng/mg cell protein per h and 1.2 micrograms/mg cell protein per h, respectively. The concentration of intracellular apo A-IV remained constant during the incubation. Insulin stimulated the production of albumin, but inhibited the production of apo A-IV dose-dependently. Glucagon inhibited the production of both albumin, and apo A-IV dose-dependently. Dexamethasone showed no significant effects on albumin production, but stimulated apo A-IV production. Thus, apo A-IV production in hepatocytes is regulated by several hormones with different effects on albumin production. The regulatory effects of these hormones on apo A-IV production were almost identical with the effects observed in a course of apo A-I synthesis, suggesting that the production of the two apoproteins are regulated by similar mechanisms.
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PMID:Effect of insulin, glucagon or dexamethasone on the production of apolipoprotein A-IV in cultured rat hepatocytes. 185 65

We studied the effect of insulin, glucagon or dexamethasone on the production of insulin-like growth factor I (IGF-I) by cultured rat hepatocytes. Hepatocytes were isolated from normal adult rat livers and cultured in MEM, as nearly confluent monolayers. In the absence of such hormones, IGF-I and albumin accumulated in the culture medium almost linearly for periods up to 24 hours with the accumulation rates of 140 mU/mg cell protein per hour and 1.2 micrograms/mg cell protein per hour, respectively. Cycloheximide (5 micrograms/ml) almost completely inhibited the accumulation of IGF-I and albumin in the medium. Insulin at concentrations over 10(-10) M significantly inhibited the production of IGF-I in spite of the increased production of albumin. Conversely, glucagon stimulated the production of IGF-I at concentrations over 10(-8) M, but inhibited the production of albumin at concentrations over 10(-10) M. Dexamethasone stimulated the production of IGF-I at concentrations over 10(-7) M, but had no significant effects on the production of albumin. Thus, IGF-I production of hepatocytes is regulated by several hormones with different manner from albumin production.
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PMID:Effect of insulin, glucagon or dexamethasone on the production of insulin-like growth factor I in cultured rat hepatocytes. 206 Aug 98

Dexamethasone can promote the differentiation of different tissues in vivo while dimethylsulfoxide is a commonly used inducer of differentiation in various tumor cell types in culture. In the present study, the effects of dexamethasone and dimethylsulfoxide on growth and functional activities of cultured differentiating suckling rat hepatocytes stimulated with various combinations of EGF, insulin, and glucagon were evaluated. Hepatocytes stimulated with EGF and either insulin or glucagon entered S phase and mitosis after a lag period of 24 h. These hormonal factors thus provide simple combinations of hepatocyte-growth regulators. Dexamethasone in the presence of EGF and glucagon inhibited the initiation of DNA synthesis and mitosis, but it had no effect on EGF-insulin stimulated cultures. Such a differential effect of dexamethasone was observed at concentrations ranging from 4 nM to 200 microM. alpha-Fetoprotein, albumin, and tyrosine aminotransferase were used as typical markers of hepatocyte differentiation status. Irrespective of the combinations of growth-promoting factors used, dexamethasone inhibited alpha 1-fetoprotein production and maintained albumin production and tyrosine aminotransferase inducibility. In contrast, dimethylsulfoxide at 2% inhibited hepatocyte growth and supported the maintenance of the production of both alpha 1-fetoprotein and albumin, independent of the hormonal growth regulators used. On this basis, dexamethasone and dimethylsulfoxide act as distinct modulators of growth and maturation of cultured differentiating suckling rat hepatocytes.
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PMID:Dexamethasone and dimethylsulfoxide as distinct regulators of growth and differentiation of cultured suckling rat hepatocytes. 242 23

To evaluate the possible role of various hormones on fetal pancreas development, late gestational fetal rat pancreata (20 days) were cultured in a serum-free medium for 6 days in the presence of cholecystokinin-octapeptide (CCK-8), epidermal growth factor, triiodothyronine, or glucagon with or without dexamethasone. In the absence of any added hormone, the tissue amylase activity declined very rapidly. Epidermal growth factor alone (4.10(-7) M) could not preserve the amylase activity, whereas triiodothyronine (0.1 microM) and glucagon (4 micrograms/ml) had a deleterious effect that was prevented by the addition of DXM (3.10(-6) M). In the presence of CCK-8 (2.10(-11) M) 50 and 30% of the amylase activity was maintained on the 2nd and the 4th day of culture, respectively. The CCK-8 effect was dose dependent and was inhibited by asperlicin (10 microM). The combination of CCK-8 and dexamethasone maintained more than 80% of the amylase activity in the fetal pancreas explants through 4 days of culture. Fetal pancreas cultured in this optimal medium and treated with streptozotocin (10(-7) M) during the 1st day of culture showed a significantly lower tissue amylase activity on the 4th and 6th days than those not treated with streptozotocin. The streptozotocin effect was attenuated when insulin (0.1 U/ml) was added. These data suggest that, in addition to the well-known effect of glucocorticoid on enzyme activities in the fetal pancreas, two additional hormones, CCK and insulin, could play a role in the modulation of pancreatic amylase activity in the fetal rat.
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PMID:The effect of cholecystokinin-octapeptide, insulin, glucagon, triiodothyronine, and epidermal growth factor on amylase activity in fetal pancreas in vitro. 245 67

Lipogenesis in isolated fetal hepatocytes in suspension for 3 h was modulated by insulin depending on substrates utilization, but was inhibited by glucagon and noradrenaline from all substrates studied. After primary culture for 5 days in the presence of glucose, the lipogenic response to insulin increased, the glucagon response decreased and noradrenaline produced the same degree of inhibition at 3 h. At 24 h, insulin produced an even higher increase on lipogenesis parallel to an increase in fatty acid synthase activity. Dexamethasone increased lipogenesis, but progesterone had no effect. Both hormones, in the presence of insulin, increased lipogenesis and fatty acid synthase activity. Triiodothyronine, alone or in the presence of insulin, increased lipogenesis and fatty acid synthase activity.
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PMID:Rates of lipogenesis in fetal hepatocytes in suspension and in primary culture: hormonal effects. 266 43

In the liver of suckling rats, the synthesis of hepatic tyrosine aminotransferase, serine dehydratase, and phosphofructokinase 2 as well as of renal beta-glucosidase is controlled by the circulating concentrations of adrenal and pancreatic hormones. Glucagon is capable of stimulating enzyme synthesis only in the presence of a steroid hormone. Dexamethasone and estradiol have been found to exert a permissive function on the inducibility of the studied enzymes by glucagon. Between the hormones of the adrenal medulla and glucagon antagonistic effects in enzyme induction were observed. Obviously, this antagonism is mediated by the alpha 1-adrenergic signal transferring system. A characteristic age dependence of enzyme induction by dexamethasone has been established. This might be correlated to alterations in the degree of methylation of the respective promoters. The methylation inhibitor 5-azacytidine influences significantly the enzyme induction by glucocorticoid hormones.
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PMID:Interaction of adrenal and pancreatic hormones in the control of hepatic enzymes during development. 289 Feb 81

The aims of this study were to investigate the control of fatty acid synthesis and its relationship to surfactant production in the fetal lung during alteration of hormonal and substrate conditions. Lung explants from 18 day fetuses (term = 22 days) which were cultured 2 days in the presence of 10 mM lactate showed parallel acceleration of de novo fatty acid synthesis (3H2O incorporation) and [14C]choline incorporation into disaturated phosphatidylcholine (DSPC) compared to culture of explants in glucose. Both the cultured and fresh explants were resistant to the classical short term (4 h) cAMP inhibition of fatty acid synthesis with 3 mM dibutyryl cAMP or 0.5 mM aminophylline. In the cultured explants short term cAMP elevation increased DSPC production, and long term (2 day) cAMP elevation caused a further increase in DSPC synthesis and also stimulated fatty acid synthesis. In cultured explants from 17 day fetuses, dexamethasone (0.1 microM) caused a synergistic increase with aminophylline in both fatty acid synthesis and DSPC production whereas, in explants from 18 day fetuses, dexamethasone inhibited both processes and reduced the level of stimulation of DSPC and fatty acid synthesis seen with aminophylline alone. Dexamethasone also reduced the stimulation of both DSPC and fatty acid synthesis produced in the culture of 18 day explants with bacitracin (0.5 mg/ml), whereas the combination of bacitracin and aminophylline resulted in a synergistic increase in DSPC production. Culture with glucagon (0.1 microM) also stimulated DSPC synthesis but at physiological levels insulin had no effect on either DSPC or fatty acid synthesis. These data show that lung fatty acid synthesis exhibits unique features of fatty acid synthesis regulation compared to other lipogenic tissues and also suggest a link between de novo fatty acid synthesis and surfactant production during the critical period of accelerated lung maturation.
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PMID:Fatty acid synthesis in the fetal lung: relationship to surfactant lipids. 301 23


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