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)

Liver cells isolated from newborn rats and seeded on a non-adherent plastic substratum were found to spontaneously re-aggregate and to form, within a few days, spheroidal aggregates that eventually reached a plateaued diameter of 150-175 micron. Analyses on frozen sections from these spheroids by immunofluorescence microscopy using antibodies to various cytoskeletal elements and extracellular matrix components revealed a sorting out and a histotypic reorganization of three major cell types. A first type consisted of cells that segregated out on the aggregate surface forming a monolayer cell lining; a second type was identified as hepatocytes that regrouped in small islands often defining a central lumen; and a third group of cells reorganized into bile duct-like structures. This intercellular organization in the aggregates was paralleled by the accumulation of extracellular matrix components (laminin, fibronectin, and collagen) and their deposition following a specific pattern around each cell population structure. Determinations of albumin secretion and tyrosine aminotransferase induction by dexamethasone and glucagon at various times after the initiation of the cultures revealed a maintenance of the hepatocyte-differentiated functions for at least up to 2 mo at the levels measured at 3-5 d. It is concluded that cells dispersed as single cells from newborn rat liver conserve in part the necessary information to reconstruct a proper three-dimensional cyto-architecture and that the microenvironment so generated most likely represents a basic requirement for the optimal functioning of these differentiated cells.
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PMID:Spheroidal aggregate culture of rat liver cells: histotypic reorganization, biomatrix deposition, and maintenance of functional activities. 241 40

The absorption of zinc is increased when the dietary zinc supply is low. This is caused by increased intestinal transport and reduced secretion of endogenous zinc into the intestine. Kinetic analysis of zinc transport, based on data from either the isolated perfused intestine or brush border membrane vesicles, demonstrates uptake velocity is increased homeostatically by a carrier-mediated phase of transport in response to low dietary zinc. Zinc within intestinal cells binds to high molecular weight proteins and metallothionein. Expression of the metallothionein gene is altered by zinc status and the protein appears to have a function in intestinal cells. Zinc transport across the basolateral membrane is also carrier-mediated and may be ATP-driven. Newly absorbed zinc is transported via albumin, first to the liver and then is redistributed to other tissues, particularly muscle and bone which provide the greatest reserves. Plasma zinc levels remain relatively constant except during periods of dietary zinc depletion and acute responses to stress, infection or inflammation where they are depressed. Experiments with intact rats and isolated rat liver parenchymal cells have shown that hepatic zinc turnover is rapid. Stimulation of liver cells by glucocorticoids, glucagon, epinephrine, cAMP or interleukin-1-like factors alters uptake/exchange kinetics such that there is a net accumulation of cellular zinc. Metallothionein gene expression is enhanced by these hormonal signals, and a considerable portion of the newly accumulated zinc is accounted for as that associated with this zinc-binding protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Toward a molecular understanding of zinc metabolism. 242 May 2

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

We have recently shown that a variety of proteins, including albumin and immunoglobulins conjugated to colloidal gold, strongly binds to certain basic peptide sequences, and neurohormonal peptides. Silver proteinate, used in the classical Bodian's neurohistological procedure, is now shown to bind to the same peptide sequences in cytochemical model systems. In tissue, gastrin cells and glucagon cells have been reported to show strong unspecific immunocytochemical staining and these cell types also stain in the Bodian's procedure. These results suggest that certain types of unspecific immunocytochemical staining and the Bodian's silver staining method may depend upon a common mechanism, involving binding of labelled or aggregated protein to basic and hydrophobic sequences in tissue.
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PMID:Bodian's silver impregnation of endocrine cells. A tentative explanation to the staining mechanism. 243 38

Biochemical functions of human livers were studied using fetal hepatocytes in primary culture. Immunocytochemical staining showed that albumin was not expressed in any fetal hepatocytes, whereas alpha-fetoprotein was detected in almost all the cells. Tryptophan 2,3-dioxygenase (TO, EC 1.13.11.11.) activity was not induced in the presence of 10(-7) M dexamethasone and 10(-7) M glucagon, but the activity of tyrosine aminotransferase (TAT, EC 2.6.1.5.) was elevated about 35 fold under the same conditions. These results suggest that the TAT and alpha-fetoprotein genes are activated in human fetal liver at 14 to 20 weeks of gestation.
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PMID:Studies on the expression of liver-specific functions of human fetal hepatocytes in primary culture. 244 88

Effect of glucagon on energy-metabolite transport into cardiac muscle was studied during a single transit through the isolated rabbit heart using a rapid paired-tracer dilution method. Kinetic experiments revealed that 1.5 microM glucagon stimulated the influx of palmitate bound to 30 g/litre albumin, by increasing the V 2.3 times and increasing the Km for transport 2.4 times. Tracer uptake of D-glucose, as the only exogenous substrate provided, was increased by 80% by 1.5 microM glucagon. Myocardial utilization of [3H]-or [14C]-labelled short-chain monocarboxylic acids (L-lactate, pyruvate and acetate) was significantly reduced by glucagon, to the same degree as their unidirectional sarcolemmal transport. Inhibition of L-[14C]lactate uptake was dose-dependent and in positive correlation with myocardial lactate production. It is concluded that glucagon may regulate sarcolemmal permeability and myocardial utilization for energy-metabolites from the coronary circulation.
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PMID:Glucagon effect on myocardial transport and utilization of energy-metabolites from the coronary microcirculation in the perfused rabbit heart. 246 51

Hepatocytes were isolated by application of the two-step collagenase perfusion technique to pieces of human liver. The cells were incubated in serum-free medium or 10% FCS-medium supplemented with insulin, glucagon and dexamethasone, and kept in culture for more than 2 weeks. Seventy-five per cent of the medium was changed regularly and assayed for alpha 2-macroglobulin (alpha 2-M), pregnancy zone protein, alpha 1-antitrypsin and albumin by means of ELISA. Significant amounts of alpha 2-macroglobulin were present in all cultures. During incubation, alpha 2-M accumulated in the medium and the quantity of alpha 2-M released from the cells by far exceeded protein associated with hepatocytes prior to incubation. In 24 h 10(6) hepatocytes secreted 160.5 +/- 82.2 ng of alpha 2-M (mean +/- SD, n = 5). Cell-associated, as well as secreted alpha 2-M appeared to be on native form, as determined by immunoisolates from lysed cells and culture supernatants. Pregnancy zone protein was only detected in about 50% of the cultures and its rate of secretion was less than 2 ng 24 h-1 per 10(6) cells. In contrast, culture medium contained considerable quantities of alpha 1-antitrypsin and albumin. In 24 h, 10(6) hepatocytes released greater than 2 micrograms alpha 1-antitrypsin and greater than 5 micrograms albumin. The present study suggests the hepatocyte to be of major importance for the synthesis of intravascular alpha 2-M.
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PMID:Synthesis and secretion of alpha 2-macroglobulin by human hepatocytes in culture. 246 99

The records of 57 patients with acute viral hepatitis (28 given hormones and 29 placebo) in a double blind controlled trial of one week of glucagon and insulin therapy were analyzed. In the placebo group, SGPT values dropped after treatment with improved prothrombin time and serum levels of total bilirubin and albumin. In the hormone group, they changed similarly, except serum albumin levels which were reversed during treatment (P less than 0.05). There was a bottom line of serum albumin levels which preceded a peak of serum alpha-fetoprotein levels within one week in the placebo group, but was around the peak in the hormone group. There were 12 patients in the hormone group in whom serum alpha-fetoprotein levels rose with treatment and decreased after its discontinuation, and 5 in the placebo group (P less than 0.05). Such a change in serum alpha-fetoprotein levels was accompanied by decreased serum albumin levels in 6 of 10 patients given hormones and none of the 5 given placebo (P less than 0.05). These results indicate reciprocal changes in serum albumin and alpha-fetoprotein levels appearing during the recovery course of acute viral hepatitis, and suggest that this therapy may stimulate its development. Stimulation of liver regeneration by this therapy merits consideration.
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PMID:Reciprocal changes in serum albumin and alpha-fetoprotein levels in the recovery course of acute viral hepatitis stimulated by glucagon and insulin therapy: analysis of a double blind controlled trial. 247 94

Cultured human fetal liver explants were used to study regulation of the GH-independent insulin-like growth factor-binding protein (BP-28). BP-28 was produced by fetal liver explants at approximately 200 ng/mg total tissue protein.day between days 3 and 6 in culture and was inhibited 60% after 3-day exposure to cycloheximide (10 micrograms/mL). BP-28 production was stimulated over 3-fold by 20 mmol/L theophylline, over 2-fold by 30 mumol/L forskolin, and 90% by 10 micrograms/mL glucagon. The glucose concentration in the medium inversely regulated BP-28 production, which was 68% higher in 2 mmol/L glucose than in 30 mmol/L glucose (P less than 0.001); in contrast, albumin production was 40% lower in 2 mmol/L glucose than in 30 mmol/L (P less than 0.05). BP-28 levels were inhibited 50% by 300 nmol/L insulin or 3 mumol/L dexamethasone. In acid extracts of cultured tissue, BP-28 levels were less than 10% of the amount secreted in 48 h. These results are consistent with the conclusion that intracellular glucose availability is an important regulator of hepatic BP-28 synthesis.
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PMID:Regulation of growth hormone-independent insulin-like growth factor-binding protein (BP-28) in cultured human fetal liver explants. 247 91

The mediator(s) and mechanism(s) of acute-phase protein synthesis in the liver following injury and sepsis are not fully known. Elevated plasma levels of the catabolic hormones cortisol, glucagon, and epinephrine have been reported in trauma and sepsis. In previous reports, when these hormones were infused simultaneously (triple hormone infusion), several, but not all, of the metabolic alterations characteristic of sepsis occurred. In the current investigation, the effect of triple hormone infusion on hepatic protein synthesis was studied. Rats were infused intravenously during 16 hours with a solution containing corticosterone (4.2 mg/kg/h), glucagon (2.5 micrograms/kg/h), and epinephrine (6 micrograms/kg/h). Control animals were infused with a corresponding volume of vehicle. Total hepatic protein synthesis in vivo was measured with a flooding dose technique using [14C]-leucine. The synthesis of total secretory proteins and of the individual proteins albumin, complement component C3, and alpha 1-acid glycoprotein was measured in isolated, perfused liver using [3H]-leucine and a recirculating technique. Urinary excretion of nitrogen and plasma concentration of glucose were higher and plasma total amino acid concentration was lower in hormone-infused than in control rats. Total hepatic protein synthesis in vivo, expressed as the proportion of the protein pool that was replaced each day, was increased from 39% +/- 2% per day to 48% +/- 3% per day (P less than .05) by hormone infusion, but synthesis of secretory proteins in perfused liver was not significantly altered. The results suggest that although total hepatic protein synthesis may be increased by catabolic hormones, other mediator(s) are probably responsible for the stimulation of acute-phase protein synthesis in sepsis.
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PMID:Protein synthesis in liver following infusion of the catabolic hormones corticosterone, epinephrine, and glucagon in rats. 247 64


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