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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The isolated rat liver perfused for 12 hours at pH 7.10 with a suspension of bovine erythrocytes in Krebs-Ringer bicarbonate buffer containing 3 per cent bovine serum albumin has been used as a test system to study effects of glucagon and of dexamethasone in the presence and absence of insulin on net biosynthesis of rat serum albumin, fibrinogen, alpah1-acid glycoprotein, alpha2-(acute phase) globulin, and haptoglobin. Quantitative measurement of perfusate glucose, amino acid nitrogen, and urea affords a basis for determining net glucose and nitrogen balance in the perfusion system. Although the dose of dexamethasone (total 1.0 mug.) used was insufficient to induce synthesis of alpha2-acute phase globulin, net syntheses of albumin, fibrogen, alpha1-acid glycoprotein, and haptoglobin were increased. Glucagon given with dexamethasone depressed albumin and haptoglobin synthesis markedly, but not that of fibrinogen and alpha1-acid glycoprotein. Glucagon with dexamethasone markedly enhanced ureogenesis and glycogenolysis and elicited an exaggerated negative nitrogen balance. The unfavorable effects of glucagon on albumin and haptoglobin synthesis and on nitrogen balance were reversed by giving insulin simultaneously. It is emphasized that insulin is essential for positive nitrogen balance.
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PMID:Direct effects of glucagon on protein and amino acid metabolism in the isolated perfused rat liver. Interactions with insulin and dexamethasone in net synthesis of albumin and acute-phase proteins. 6 Nov 40

Low-molecular weight dialysable peptides, obtained by plasmin degradation of purified bovine fibrinogen preparations, have been shown to increase the chronotropic activity of isolated rat atria. This effect was dose dependent and was inhibited by inhibitors of glycolysis (NaF and 2-deoxy-D-glucose), but not by an inhibitor of oxidative phosphorylation (2, 4-dinitrophenol). Propranolol, a beta-blocking agent, was also ineffective. Fibrinogen-derived peptides increased both cAMP levels and phosphorylase alpha activity in stimulated atria. The increase of these parameters was transitory and appeared to precede the occurrence of the positive chronotropic effect. In the test situation used, the biochemical and functional modifications induced by fibrinogen-derived peptides were similar to those induced by glucagon.
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PMID:Positive chronotropic effect of dialysable peptides derived from plasmin digestion of bovine fibrinogen preparations. 17 24

The hepatic tolerability of phthalazine-(2,2-b)-phthalazin-5,12-(7H,14H)-dione (diftalone--administered at the dosage of 750 mg/day p.o. for a mean period of 23 days--has been studied in 40 patients by means of: total plasma protein, albumin, fibrinogen, serum glutamin-oxalacetic transaminase, serum glutamic-pyruvic transaminase, lactic dehydrogenase, creatine phosphokinase, alkaline phosphatase, glycemic curve after glucagon and plasmatic elimination of bromosulphalein. A statistically but not clinically significant increase of the SGPT level is the only change observed.
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PMID:Some laboratory aspects of hepatic tolerability of diftalone. 57 43

Liver parenchymal cells were isolated from adult rats by digesting liver slices or perfusing liver with collagenase. The cell yields were 1.5 X 10(7) and 1.0 X 10(8) cells/g liver from slices and perfused liver, respectively, and in both cases the cell viabilities and attachment efficiencies were over 90% and 60%, respectively. The cells were viable for more than one week when cultured in Williams medium E with 10% fetal bovine serum, and addition of insulin and dexamethasone enhanced the maintenance of cell viability. Various biochemical functions or freshly isolated cells and cultured cells were compared in this medium. In freshly isolated cells, induction of tyrosine transaminase [EC 2.6.1.5] by dexamethasone was low and none of the hormones examined stimulated protein synthesis; but when the cells had been cultured for a few days, induction of tyrosine transaminase became prominent, and insulin and dexamethasone stimulated protein synthesis and glucagon inhibited their effect. About half the synthesized proteins were secreted into the medium and among these proteins, albumin, transferrin, fibrinogen, and lipoproteins were identified immunochemically and electrophoretically. It was also shown that the polysomes in freshly isolated cells were almost completely disaggregated, but that in cells after a few days culture they were reaggregated. These results showed that freshly isolated cells have impaired functions, but that after culture for a few days the cells recover various liver functions and thus become more suitable for use in biochemical studies on liver functions.
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PMID:Biochemical studies on liver functions in primary cultured hepatocytes of adult rats. I. Hormonal effects on cell viability and protein synthesis. 71 6

A system using hepatocyte suspensions in vitro was developed for studying the synthesis of albumin, fibrinogen and transferrin. Conditions for optimum survival of the hepatocyte and for synthesis of these plasma proteins were defined for this system. These conditions included the use of horse serum (17.5 percent, v/v, heat-inactivated), an enriched medium (Waymouth's MB 752/1), an O2 tension of between 18.7 times 10(3) and 26.7 times 10(3) Pa and constant stirring. Albumin, fibrinogen and transferrin synthesis rates were obtained of 0.32 p 0.094(10), 0.12 p 0.030(11) and 0.097 p 0.017(10) [mean p S.D. (n)]mg/h per g of hepatocytes respectively. These rates were maintained for the first 12h of study and synthesis continued at a diminished rate up to 48h. The synthesis of albumin was decreased in a medium containing less amino acids and glucose, but that of fibrinogen was substantially unaffected. ATP concentrations up to 12h and RNA/DNA ratios up to 24h were comparable with values in vivo. The ability to study cells up to 48h permitted us to find that the addition of a mixture of hormones consisting of glucagon, cortisol, tri-iodothyronine and growth hormone enhanced fibrinogen synthesis. Addition of insulin to the above mixture resulted in increased synthesis for albumin and transferrin but not for fibrinogen.
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PMID:Albumin, fibrinogen and transferrin synthesis in isolated rat hepatocyte suspensions. A model for the study of plasma protein synthesis. 114 94

The rate of hemopexin synthesis in adult rat hepatocyte suspension (0.17 +/- 0.019 (6)) (mean +/- SEM (n) mg/g hepatocytes per hour) was found to be linear for 48 h. By contrast, the rate of synthesis of albumin and fibrinogen was close to linear for only 12 h after which it continued at a diminished rate. Supplementation of the incubation medium with insulin, cortisol, glucagon, triiodothyronine, and growth hormone affected no significant increase in the synthesis rate of hemopexin but by contrast did do so in that of albumin (22%) and of fibrinogen (123%) (although not to the point of causing these last to become linear). The pattern of hemopexin synthesis and its response to hormones is clearly different from that observed with other plasma proteins studied in this hepatocyte system. Hempoexin synthesis appeared to be at its maximum and to be independent of hormone supplementation, and it was continuing linearly at a time when the synthesis of other plasma proteins was falling.
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PMID:Synthesis of hemopexin with and without hormonal supplementation in rat hepatocyte suspensions: comparison with that of albumin and of fibrinogen. 125 85

It has been suggested recently that patients with fulminant liver failure should be prepared for transplantation by early hepatectomy, yet the acute effects of removal of the liver upon the coagulation profile and certain hormones are not known. This study was conducted on totally hepatectomized pigs that survived up to 27 hr. Measurements were made of serum insulin, plasma glucagon (IRG and GLI), glucose, catecholamines, and the coagulation profile. The increase in serum insulin was directly related to levels of plasma glucose--there was a 100-fold increase in animals with plasma glucose levels greater than 400 mg/100 ml and none when blood glucose was less than 100 mg/100 ml. Plasma glucagon showed a sharp transient increase within 1 hr of hepatectomy and a slow rise thereafter with levels apparently unrelated to serum insulin or plasma glucose. There was a transient increase in plasma adrenaline but a sharp continuous increase in plasma norepinephrine. No changes of note occurred in the coagulation profile--even levels of fibrinogen only declined by 20% in 27 hr. The study has shown that early total hepatectomy is safe as far as changes in coagulation are concerned but changes in serum insulin and especially plasma norepinephrine may be of more significance.
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PMID:Effect of total hepatectomy on coagulation and glucose homeostasis in the pig. 173 54

An arginine esterase was purified from the venom of Vipera lebetina by gel filtration on Sephadex G-100 and by affinity and DEAE-cellulose chromatography. The enzyme has a mol. wt of 52,500 and pI approximately 3. It is a glycoprotein containing 23% of neutral sugars, and has extremely high thermostability. The esterase activity is inhibited by diisopropylfluorophosphate (DFP) and phenylmethylsulfonyl fluoride (PMSF). The Km and kcat values are for alpha-N-benzoyl-L-arginine ethyl ester (BAEE) 7.7 x 10(-5) M and 43.8 sec-1, for p-tosyl-L-arginine methyl ester (TAME) 3.6 x 10(-4) M and 39.8 sec-1 (pH 8.5, 25 degrees C, and for alpha-N-benzoyl-DL-arginine-4-nitroanilide (BAPNA) 1.8 x 10(-4) M and 0.94 sec-1 (pH 8.3, 25 degrees C), respectively. Lysine esters are not hydrolyzed. The enzyme has weak caseinolytic activity and hydrolyzes glucagon at the sites Lys12-Tyr13, Arg17-Arg18 and Arg18-Ala19. In fibrinogen it cleaves B beta-chain first and later also the A alpha-chain.
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PMID:Beta-fibrinogenase from the venom of Vipera lebetina. 202 69

High yields of human hepatocytes (up to 23 X 10(6) viable cells/g) were obtained from small surgical liver biopsies (1 to 3 g) by a two-step collagenase microperfusion method. Cell viability was about 95%, attachment efficiency of hepatocytes seeded on fibronectin-coated plates was 80% within 1 h after plating, and cells survived for about 2 wk in serum-free Ham's F12 containing 0.2% bovine serum albumin, 10(-8) M insulin, and 10(-8) M dexamethasone. To evaluate the metabolism of human hepatocytes in serum-free conditions, we measured their most characteristic biochemical functions and compared them to those reported for human liver. After 24 h in culture, glycogen content was 1250 +/- 177 nmol glucose/mg cell protein and remained stable for several days. Gluconeogenesis from lactate in hormone-free media was (3.50 +/- 0.17 nmol glucose.mg-1.min-1) similar to that reported for human liver. Insulin at 10(-8) M activated glycolysis (X1.40) and glycogenesis (X1.34), and glucagon at 10(-9) M stimulated gluconeogenesis (X1.35) and glycogenolysis (X2.18). Human hepatocytes synthesized albumin, transferrin, fibrinogen, alpha 1-antitrypsin, alpha 1-antichymotrypsin, alpha 1-acid glycoprotein, haptoglobin, alpha 2-macroglobulin, and plasma fibronectin and excreted them to the culture medium. Maximum protein synthesis was stimulated by 10(-9) M dexamethasone. Basal urea synthesis oscillated between 2.5 and 3.5 nmol.mg-1 cell protein.min-1, about 5 times the value estimated for human liver. Cytochrome P-450 decreased in culture but it was still 20% of freshly isolated hepatocytes by Day 5 in culture. In addition, ethoxycumarin-O-deethylase and aryl hydrocarbon hydroxylase could be induced in vitro by treatment with methyl cholanthrene. Glutathione levels were similar to those reported for human liver (35 nmol.mg-1). The results of our work show that adult human hepatocytes obtained from small surgical biopsies and cultured in chemically defined conditions express their most important metabolic functions to an extent that is similar to that reported for adult human liver.
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PMID:Culture of human hepatocytes from small surgical liver biopsies. Biochemical characterization and comparison with in vivo. 215 94

The mechanisms that regulate collagen gene expression in hepatic cells are poorly understood. Accelerated Ca2+ fluxes are associated with inhibiting collagen synthesis selectively in human fibroblasts (Flaherty, M., and Chojkier, M. (1986) J. Biol. Chem. 261, 12060-12065). In suspension cultures of isolated hepatocytes, the Ca2+ agonist vasopressin increases cytosolic levels of free Ca2+ (Thomas, A.P., Marks, J.S., Coll, K.E., and Williamson, J. R. (1983) J. Biol. Chem. 258, 5716-5725). However, whether vasopressin's interactions with plasma membrane V1 receptors attenuate hepatic collagen production is unknown. We investigated this problem by studying vasopressin's effects on collagen synthesis and Ca2+ efflux in long-term primary cultures of differentiated and proliferation-competent adult rat hepatocytes. Twelve-day-old quiescent cultures were exposed to test substances and labeled with [5-3H]proline. Determinations of radioactivity in collagenase-sensitive and collagenase-resistant proteins were used to calculate the relative levels of collagen production. Synthetic [8-arg]vasopressin stimulated 45Ca2+ efflux within 1 min and inhibited hepatocyte collagen production within 3 h by 50%; overall rates of protein synthesis were not affected significantly. In cultures labeled with [35S]methionine, vasopressin also decreased the levels of newly synthesized and secreted albumin, but not fibrinogen, detected in specific immunoprecipitates analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Northern blot analyses using specific [32P]cDNA probes revealed 70% decreases in hybridizable levels of collagen alpha 1(I) mRNA in hepatocyte cultures treated with either vasopressin or Ca2+ ionophore A23187; hybridizable levels of albumin mRNA also fell approximately 50% following vasopressin treatment. Vasopressin did not affect collagen production in quiescent cultures of mouse Swiss 3T3, human myofibroblast or rat smooth muscle cells; and hepatocyte collagen production was unaffected by treatment with glucagon or dibutyryl cAMP. Thus, accelerated Ca2+ fluxes induced by vasopressin are associated with decreased production of hepatocyte collagen and albumin in primary cultures that simulate quiescent adult rat liver.
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PMID:Vasopressin inhibits type-I collagen and albumin gene expression in primary cultures of adult rat hepatocytes. 254 14


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