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

Concanavalin A inhibits the (Na+-K+)-ATPase activity of isolated rat-liver plasma membranes, while leaving the Mg2+-ATPase unaffected. Glucagon and cyclic AMP act supplementary to the lectin in the inhibition. The lectin effect is counteracted by insulin and L-epinephrine, and is completely abolished by the beta-adrenergic blocking agent propranolol. Results are discussed on the basis of the known interactions of concanavalin A with plasma membrane components, including its hormone-like action.
 ...
PMID:Studies on plasma membranes. XXIII. Hormone-like action of concanavalin A on liver plasma membranes: inhibition of (Na+-K+)ATPase. 12 72

Insulin action is discussed with emphasis on events that occur at the plasma membrane. A summary is presented of previous studies which indicate that the insulin receptor of fat and liver cells is a large glycoprotein, partially buried in the outer surface of the plasma membrane, with a high (K-D approximately 10-10 M) and specific affinity for insulin. The participation of membrane phospholipids in the binding of insulin and the role of sialic acid residues in the transmission of the insulin binding signal are discussed. The relation of insulin action to its effects on cyclic nucleotide levels is explored. On the one hand, insulin action (glucose transport) is inhibited by compounds (cholera toxin, ACTH, glucagon and L-norepinephrine) that stimulate adenylate cyclase; conversely, insulin both inhibits the lipolytic action of these compounds, and raises cellular levels of cyclic GMP. An hypothesis is presented whereby a single cyclase species may be responsible for the formation of either cyclic AMP or cyclic GMP, depending on the nature of the hormone stimulus. The role of membrane phosphorylation in the action of insulin is discussed in the context of experiments demonstrating a specific inhibition by ATP of insulin-mediated glucose transport, in association with the phosphorylation of two specific membrane proteins. The ability of insulin to modulate cyclic nucleotide levels in cultured cells and to act as a growth factor is discussed. Insulin stimulates DNA synthesis and the uptake of alpha-aminoisobutyric acid in human fibroblasts, which effects are also mediated by epidermal growth factor. Insulin acts at concentrations much higher than those obtained in vivo, whereas epidermal growth factor acts at concentrations thought to be physiological. The insulin binding sites (K-D is approximately equal to 10-9 M) related to growth, and observed both in human fibroblasts and in lectin-stimulated and leukemic human lymphocytes would not be appreciably occupied at physiological insulin concentrations. The implications of such 'low affinity' binding sites for insulin are discussed in relation to the action of other growth factors.
 ...
PMID:Insulin: interaction with membrane receprots and relationship to cyclic purine nucleotides and cell growth. 16 82

Lectins from Agaricus bisporus and Agaricus campestris stimulate insulin and glucagon release from isolated rat islets in the presence of 2 mM glucose. In the case of insulin release, maximal stimulation was observed at lectin concentrations above 58 mug. per milliliter (approximately 1 muM).A. bisporus PHA-B-stimulated insulin release was independent of a source of metabolic energy but was abolished by deuterium oxide. The lectin did not alter islet glucose oxidation to CO2 or incorporation of [3H] leucine into trichloracetic acid-precipitable material nor did it modify rates of insulin secretion induced by 20 mM glucose. None of nine other lectins tested stimulated insulin release, whereas stimulation of fat cell glucose oxidation was a general property of the lectins. Binding of 125I-labeled A. bisporus PHA-B to islets increased with time up to one hour and after attainment of equilibrium was very slowly reversible. Binding was directly proportional to islet number and the estimated Kdiss of the binding reaction was 17 mug per milliliter. The total number of A. bisporus PHA-B binding sites per islet was approximately 2 times 10(10). Binding of A. bisporus PHA-B to the islets and A. bisporus PHA-B-stimulated insulin release were inhibited in parallel by a glycopeptide containing the oligosaccharide receptor for the lectin, suggesting that lectin binding is essential for the expression of insulin-releasing activity. It is proposed that the specific interaction between mushroom lectin and its receptors may lead to conformational changes in the structure of the membranes of the islet A2- and B-cells that facilitate exocytosis.
 ...
PMID:Effect of lectins on hormone release from isolated rat islets of langerhans. 109 48

The terminal glycoproteins of fetal, cultivated (7-12 days), and adult nondiabetic and diabetic pancreatic tissues (Balb c, C3h mice) were investigated by lectin histology (peanut-, phytohemagglutinin, wheat germ agglutinin, Ulex europeus I, concanavalin A and Ricinus communis agglutinin, PaP method +/- neuraminidase). Anti-insulin and -glucagon were used to identify islet cells. S-100 antibody showed dendritic reticulum cells, anti-IAK proved MHC II antigens (C3h). Cultured tissue was partly incubated with anti-IAK and complement for lysis of MHC II antigens. On the 19th gestational day fetal pancreatic tissue did not bind peanut agglutinin, Phytohemagglutinin, or wheat germ agglutinin, whereas concanavalin A and Ricinus communis were weakly bound. Terminal fucose residues were not expressed by C3h fetal islet cells in contrast to Balb c. Following neuraminidase digestion peanut agglutinin and phytohemagglutinin were strongly bound, indicating sialic acid-substituted terminal glycoproteins. Cultivated tissue (Day 7) bound all investigated lectins (except Ulex europeus I in C3h mice), indicating maturation of islet cells. In spite of the peak of insulin concentration in the medium we observed a faint binding of anti-insulin and investigated lectins following 12 days of cultivation. This indicates a disorder of terminal glycoprotein synthesis at this point. There was no difference in lectin binding patterns of adult nondiabetic islet cells compared to the cultivated tissue (7 days), but no Ulex europaeus I binding of the adult Balb c mice was observed. S-100 binding decreased during the cultivation period as dendritic reticulum cells became destroyed by cultivation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Lectin histochemical investigations of fetal cultivated pancreatic tissue. 140

Variation in cell-surface sugar residues which exist between different pancreatic cells has been exploited in an attempt to isolate beta-cells from dispersed porcine pancreas utilizing selective lectin binding. The binding characteristics of a range of lectins were compared to determine their ability to differentiate between endocrine and non-endocrine cells in the porcine pancreas. Histological analysis showed that peroxidase labelled Arachis hypogaea bound selectively to islet cells in Carnoy-fixed sections of pancreas. In five experiments, porcine pancreas was dispersed into single cells by collagenase digestion, incubated with fluorescein isothiocyanate-labelled Arachis hypogaea and analysed using a Fluorescence Activated Cell Sorter. Fluorescein isothiocyanate-labelled Arachis hypogaea bound to a population of cells comprising 6% +/- 4.2% (mean +/- s.d.) of the total. Cells from representative samples were sorted into populations, based on fluorescence. Immunohistochemical analysis of the fluorescent populations showed that 93% +/- 2% of these cells contained insulin: none of the cells stained positive for glucagon or somatostatin. These preliminary studies show that it is possible to separate porcine beta-cells from a dispersed cell preparation using a fluorescent labelled lectin.
 ...
PMID:Separation of beta-cells from dispersed porcine pancreas by selective lectin binding. 181 75

Active glucagon receptor was solubilized with 3-(3-cholamidopropyl)dimethylammonio-1-propanesulfonate (Chaps) from rat liver plasma membranes but rapidly (less than 8 h) lost activity. Either inclusion of 1X Hanks' balanced salt solution in the 3 mM Chaps solubilization buffer or its addition after solubilization increased the percentage of total binding attributable to specific glucagon binding from approximately 10 to greater than 80%; of great importance, it increased the stability from near zero binding at 8 h to 50% binding at 48 h (4 degrees C). Of the Hanks' solution components, either NaCl (137 mM) or CaCl2 (1.26 mM) was effective in increasing specific binding to approximately 70 and 60% respectively: Mg salts were ineffective. Soluble receptor binding activity was assayed by dextran-coated charcoal adsorption of free hormone. The assay is rapid, simple, and reproducible. It is suitable for monitoring receptor activity during purification and molecular characterization. Competition binding studies gave an IC50 value of 10-20 nM (slope factor approximately 1), with or without GTP. Dissociation assays revealed GTP sensitivity when receptors were solubilized either as glucagon-receptor complexes or free receptor. Active glucagon-receptor complexes could be eluted from wheat germ lectin-agarose: neither concanavalin A-agarose nor soybean agglutinin-agarose bind receptor. A glucagon degrading activity which co-solubilized with the receptor but did not require detergent for extraction was distinguishable from the soluble receptor not only by solubility but also by its heat stability (30 degrees C), its inhibition by bacitracin, its affinity for glucagon, its retention of activity for at least 1 week at 4 degrees C, and its size.
 ...
PMID:Stabilization of soluble active rat liver glucagon receptor. 254 42

Uremia is associated with impairment of various cell-mediated immunity functions. The effect of parathyroid hormone (PTH) - known to be elevated in uremia - on several T cell functions has been studied. Normal peripheral blood lymphocytes incubated with increasing amounts of human PTH (HPTH) or bovine PTH (BPTH) showed a considerable decrease (up to 40%) in lectin-induced lymphocytes transformation, significant decrease in helpers to suppressors ratio, and marked inhibition of E rosette formation and T11-positive cells. PTH alone showed no cytotoxic effect on lymphocytes when incubated with or without mitogens. Glucagon, in concentrations up to 10-fold those found on uremia, had no effect on T cell function. Thus the effect of PTH was specific to the hormone action. The direct effect of PTH on normal T lymphocytes and some of their immunological responses is not clear. However, the results of this study support the hypothesis that excess blood levels of PTH may play a role in the pathogenesis of the impairment of the immune response in uremia.
 ...
PMID:In vitro effect of PTH on normal T cell functions. 297 21

We have analyzed ligand-receptor complexes resulting from (i) the incubation of canine hepatic plasma membranes with [125I]iodoglucagon and (ii) subsequent gentle solubilization of receptor-bound ligand with digitonin. The complexes (molecular weight approximately equal to 500,000) retain the radiolabeled ligand during gel filtration and subsequent manipulation at 4 degrees C in the absence of covalent crosslinking. Affinity chromatography of the glucagon-receptor complexes on columns of wheat germ lectin linked to agarose resulted in two fractions, one of which was not bound by the column and the other of which was specifically eluted by N-acetylglucosamine. The presence of GTP during the incubation of plasma membranes with [125I]iodoglucagon caused about a 50% decrease in total ligand binding but affected only the ligand-receptor complexes that bound to wheat germ lectin. Moreover, it was found that the proportion of the two forms of ligand-receptor complexes identified by chromatography on wheat germ lectin depended on the degree of saturation of the membrane receptor. Thus, both the inhibition by glucagon of radiolabeled glucagon binding to membranes and the concomitantly decreased extent of association of the radiolabeled ligand with solubilized receptor complexes could be modeled in terms of two noninteracting receptor populations (having dissociation constants of about 0.35 and 4.94 X 10(-9) M). We conclude that (i) glucagon-receptor complexes formed on canine hepatic plasma membranes exist in two forms that differ after solubilization by digitonin in their avidities for wheat germ lectin, (ii) the high-and low-affinity binding of glucagon characteristic of hepatic plasma membranes arises from distinct receptor populations that probably differ in glycosylation, and (iii) the effect of GTP to decrease binding of glucagon to membranes arises from interactions of the nucleotide with the receptor complex that binds to wheat germ lectin.
 ...
PMID:Identification of distinct receptor complexes that account for high-and low-affinity glucagon binding to hepatic plasma membranes. 299 90

Calmodulin, a ubiquitous Ca2+-binding regulatory protein, is phosphorylated exclusively on tyrosine-99 in an insulin-dependent manner by wheat germ lectin-purified preparations of insulin receptors from rat adipocyte plasma membranes. Calmodulin is phosphorylated in the presence of polylysine, histone Hf2b, and protamine sulfate, but not in the absence of these cofactors or in the presence of other basic compounds known to interact with calmodulin, such as mellitin, myelin basic protein, chlorpromazine, trifluoperazine, substance P, glucagon, polyarginine, mastoparin, beta-endorphin, spermine, spermidine, and putrescine. The incorporation of 32P into calmodulin, expressed in terms of moles of phosphate per moles of calmodulin and assayed at calmodulin concentrations of 1.2 and 0.06 microM, is 0.023 + 0.002 and 0.046 + 0.006, respectively. This low stoichiometry is likely due to the relative impurity of the receptor preparation, as similar studies not shown here, using highly purified human insulin receptors, yield a stoichiometry of 1 mol phosphate/mol calmodulin. The time course of phosphorylation is characterized by a short initial lag phase of approximately 5 min, a rapid linear rate from approximately 5 to 40 min, with a steady state of 32P incorporation being approached at approximately 60 min. The K0.5 for ATP is 104 + 18 microM. Phosphorylated calmodulin is partially purified by HPLC on a C4 column using a trifluoroacetic acid/acetonitrile gradient solvent system. Phosphoamino acid analysis and limited thrombin digestion were used to determine that the site of insulin-induced phosphorylation of calmodulin is exclusively on tyrosine-99 regardless of the basic protein cofactor used. Phosphorylated calmodulin does not exhibit the characteristic Ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule. Thus, the tyrosine phosphorylation of calmodulin represents a potentially important post-translational modification altering calmodulin's ability to regulate a variety of enzymes involved in growth, differentiation, and metabolic regulation.
 ...
PMID:The in vitro phosphorylation of calmodulin by the insulin receptor tyrosine kinase. 341 47

Supernatants of peripheral blood mononuclear cells from healthy human donors stimulated with recall antigen (purified protein derivative of tuberculin) or lectin (phytohaemagglutinin) markedly inhibited the insulin release from isolated human and rat islets of Langerhans, and decreased rat islet contents of insulin and glucagon in a dose-dependent manner. A maximal effect on islet function was obtained with supernatant concentrations down to 5%. Supernatants of mononuclear cells stimulated with tuberculin were more potent than supernatants produced by lectin stimulation. Culture medium reconstituted with tuberculin or phytohaemagglutinin did not impair islet function. Electron microscopy demonstrated that supernatants were cytotoxic to islet cells. The cytotoxic mononuclear cell mediator(s) was non-dialysable, sensitive to heating to 56 degrees C, labile even when stored at -70 degrees C, but stable when lyophilised.
 ...
PMID:Mechanisms of pancreatic islet cell destruction. Dose-dependent cytotoxic effect of soluble blood mononuclear cell mediators on isolated islets of Langerhans. 353 29


1 2 3 Next >>