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)

The direct in vitro effect of caerulein on pancreatic protein synthesis and amino acid transport has been investigated. In contrast to in vivo conditions we were unable to demonstrate any effect on alpha-aminoisobutyric acid and leucine uptake and on leucine incorporation usin rat pancreatic lobules. Insulin and glucagon were therefore examined as possible mediators for the in vivo effect of caerulein. Insulin (1--5 microM) slightly enhanced AIB uptake (16% but did not change uptake and incorporation of leucine. Glucagon (0.01--1 microM) was ineffective. Both islet hormones had no influence on the formation of cyclic GMP induced by secretagogue either in rat (40% increase) or in guinea pig lobules (500% increase). It seems unlikely that the two islet hormones exert any direct effect on the exocrine pancreas and thus could serve as mediators for the in vivo synthetic effect of caerulein.
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PMID:Amino acid transport in the exocrine pancreas. IV. Do glucagon or insulin mediate the in vivo effect of caerulein on amino acid transport and incorporation? 47 31

Serum-free media containing 10-50 ng insulin, glucagon and epidermal growth factor (EGF) ml-1 stimulate adult rat hepatocyte proliferation in 10-15 day old primary liver cell cultures. The kinetics of this response simulate hepatocellular transitions that accompnay liver regeneration after 67% hepatectomy. Amiloride, a Na+ influx inhibitor, reversibly blocks these transitions in vitro (ID50 approximately 0.02 mM) and in vivo (ID50 approximately 25 mg kg-1). Inhibition is observed with other cation flux modulators, including ouabain (ID50 approximately 0.2 mM), 0.2 microM monensin and 0.2 microM nigericin, but not with 0.3 mM furosemide or tetrodotoxin. The prereplicative interval in culture (0-12 hr) is characterized by preferential cellular responsiveness to EGF (0-3 hr) followed by insulin plus glucagon (3-12 hr). Parallel culture and animal studies show that the amiloride-sensitive and prereplicative intervals coincide. In culture, a "burst" of 22Na+ influx, stimulated by peptide-supplemented media within 1 min but decreased later at 12 hr, is retarded by amiloride. This drug also blocks delayed prereplicative events involving increased amino acid "A" transport system function at 4-8 hr, and 3H-uridine and 3H-leucine incorporation into RNA and protein, respectively, at 8-12 hr. These findings suggest that at least two time-ordered processes are necessary to initiate hepatic growth fully: first, activation of Na+ flux systems by peptides similar or identical to EGF; and second, potentiation of these and subsequent cellular events by the combined action of insulin plus glucagon. [Amiloride: N-amidino-3,5-diamino-6-chloropyrazinecarboxamide; furosemide: 4-chloro-N-furfuryl-5-sulfamoylanthranilic acid; AIB: alpha-aminoisobutyric acid; ID50: administered dose giving 50% inhibition of a maximal response; dFBS: dialyzed fetal bovine serum; L.I.: 3H-dT nuclear labeling index.]
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PMID:Increased sodium ion influx is necessary to initiate rat hepatocyte proliferation. 50 19

Of all available liver cells in culture, only primary cultured hepatocytes are known to respond to glucagon in vitro. In the present study we investigated whether glucagon could stimulate amino acid transport and tyrosine aminotransferase (TAT;EC 2.6.1.5) activity (two well-characterized glucagon effects in the liver) in Fao cells, a highly differentiated rat hepatoma cell line. We found that glucagon had no effect on transport of alpha-aminoisobutyric acid (AIB; a non-metabolizable alanine analogue) nor on TAT activity, even though both activities could be fully induced by insulin [2-fold and 3-fold effects for AIB transport and TAT activity, respectively, after 6h; EC50 (median effective concentration) = 0.3 nM], or by dexamethasone (5-8-fold effects after 20 h; EC50 = 2 nM). Analysis of [125I]iodoglucagon binding revealed that Fao cells bind less than 1% as much glucagon as do hepatocytes, whereas insulin binding in Fao cells was 50% higher than in hepatocytes. The addition of dibutyryl cyclic AMP, which fully mimics the glucagon stimulation of both AIB transport and TAT activity in hepatocytes, induced TAT activity in Fao cells (a 2-fold effect at 0.1 mM-dibutyryl cyclic AMP) but had no effect on AIB transport. Cholera toxin stimulated TAT activity to the same extent as did dibutyryl cyclic AMP. These results indicate that the lack of glucagon responsiveness in cultured hepatoma cells results from both a receptor defect and, for amino acid transport, an additional post-receptor defect. Moreover, the results show that amino acid transport and TAT activity, which appeared to be co-induced by insulin or by dexamethasone in these cells, respond differently to cyclic AMP. This suggests that different mechanisms are involved in the induction of these activities by glucagon in liver.
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PMID:Glucagon resistance of hepatoma cells. Evidence for receptor and post-receptor defects. 613 31

In isolated rat hepatocytes, glucagon and cyclic AMP induce in vitro the emergence of a high affinity component of amino acid transport similar to that induced by fasting or partial hepatectomy, situations characterized by high plasma glucagon levels (10,11). This high affinity component has the properties of a pure A system, is operative for both AIB entry and AIB exodus, is dependent on de novo protein synthesis and has a rapid rate of degradation. The high affinity of this transport system, as well as its strong specificity for amino acids sharing the A mediation, represent a mechanism whereby the liver can adjust to increased needs for amino acids for gluconeogenesis, or for macromolecular synthesis. It appears from our studies that glucagon can rapidly stimulate amino acid transport through the synthesis of high affinity carriers which, in addition, are characterized by a rapid rate of degradation. This rapid turnover may be essential for enabling the hepatocyte to adjust its amino acid transport activity to varying environmental conditions.
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PMID:Hormonal regulation of amino acid transport in isolated rat hepatocytes: properties of a high affinity transport component induced by glucagon and cyclic AMP. 626 98

The effect of adrenalectomy on basal and hormone-stimulated amino-acid transport in liver was investigated by measuring the uptake of alpha-aminoisobutyric acid in freshly isolated rat hepatocytes. Adrenalectomy resulted in a 50% decrease in the transport capacity of hepatocytes; this change was accounted for by a diminution in the Vmax of a low affinity component of transport and specifically affected the A-transport system. Cortisone therapy fully restored the capacity of hepatocytes to transport amino acids. Sensitivity and responsiveness of hepatocytes from adrenalectomized animals to insulin, glucagon and dexamethasone, tested for the capacity of these hormones to stimulate AIB transport in vitro, were essentially identical with that of hepatocytes from control rats. The results support the concept of a positive (stimulatory) role of glucocorticoids in vivo, in the regulation of amino acid transport in the liver.
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PMID:Adrenalectomy decreases amino-acid transport in hepatocytes. 703 52