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 effects of glucagon in concentrations of 0.294 times 10(-6) mol/l, 1.47 times 10(-6) mol/l; 2.94 times 10(-6) mol/l, 5.8 times 10(-6) mol/l, and 1.47 times 10(-5) mol/l on the simultaneously recorded action potentials and contractions; and microsomal and sarcolemmal Na+-tk+-atpase in the myocardium of the guinea pig, rabbit, dog, and pig were investigated. Glucagon in all the concentrations produced an inhibition of the Na+-K+-ATPase associated with an increase in the contractility and shortening of the duration of action potential in dog myocardium. The increase in contraction was concentration-dependent up to a certain concentration. Inhibition of sarcolemmal ATPase was more than that of microsomal ATPase. In none of the concentrations did glucagon produce any significant changes in the Na+-K+-ATPase. In none of the concentrations did glucagon produce any significant changes in the Na+-K+-ATPase, contractility, and action potential duration in the myocardium of guinea pig, rabbit, or pig. These results suggest that glucagon-induced positive inotropic effect might be due to an increase in the Ca++ influx as a result of inhibition of membrane Na+-K+-ATPase. Shortening of the action potential duration might also be due to an increased efflux of potassium as a result of an inhibition of Na+-K+-ATPase.
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PMID:Glucagon-induced changes in the action potential, contraction, and Na+-K+-ATPase of cardiac muscle. 12 13

The present work was undertaken to study the effect of anti-insulinic and glycogenolytic factors on the oxidative desaturation of fatty acids. The effects of glucagon and dibutyryl cyclic AMP on the desaturation of linoleic acid to gamma-linolenic acid, alpha-linolenic acid to octadeca-6,9,12,15-tetraenoic acid, stearic acid to oleic acid, and eicosa-8,11,14-trienoic acid to eicosa-5,8,11,14-tetraenoic acid by rat liver microsomal preparations were investigated. Fasted rats had low desaturating activity, but refeeding a fat-free diet enhanced the activity. Administration of glucagon or dibutyryl cyclic AMP abolished the increase of the 6-desaturase activity elicited by refeeding. However, a similar effect on the 9-desaturase and 5-desaturase activity was not observed. The relationship between these effects and glucose metabolism is discussed.
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PMID:Effects of glucagon and dibutyryl adenosine 3', 5'-cyclic monophosphate on oxidative desaturation of fatty acids in the rat. 16 86

HMG CoA reductase, which catalyzes the reaction, HMG CoA + 2 NADAPH2 leads to mevalonate + CoA-SH + 2 NADP, is considered to be the rate-limiting enzyme on cholesterol biosynthetic pathway. Since a degree in activity of this enzyme is almost proportional to the rate of cholesterol synthesis from acetate, elucidation of factors that regulate reductase activity would provide insight into the control mechanisms on the cholesterol biosynthesis. In the present study, attempts were made to establish standard assay conditions of HMG CoA reductase activiy, and to qualify the factors affecting the activity of the enzyme. The results obtained were as follows: (1) As standard assay conditions of HMG CoA reductase activity, 85, muM were chosen for substrate concentration, 25-80 mug for microsomal enzyme protein, and 20 min for incubation time in a final volume of 0.1 ml. (2) HMG CoA reductase activity of rat liver microsomes was exhibited diurnal variation. The level of reductase activity at night was 4 fold higher than that of at daytime. (3) Either ATP or insulin administration stimulated hepatic HMG CoA reductase activity. But, cyclic AMP had no effect on reductase activity. The stimulatory effect of ATP or insulin on reductase activity was inhibited by a preadministration of glucagon. These results suggested that an interplay of hormone might regulate reductase activity and consequently cholesterol biosynthesis. (4) HMG CoA reductase activity was increased by preincubation of microsomes with cytosol. Presence of ATP or Mg++ intensified this effect. When digested by trypsin or degenerated by heat treatment, cytosol lost the stimulating activity. These results suggested as existence of protein factors in cytosol, which might modulate the enzyme interconversion from inactive to active forms.
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PMID:[Studies on the regulatory factors of 3-hydroxy-3-methylglutaryl CoA reductase (HMG CoA reductase) activity]. 18 33

Human peripheral lymphocytes were broken in a Dounce homogenizer and subcellular fractions enriched in plasma membranes or microsomal particles and mitochondria were isolated by centrifugation through a discontinuous sucrose gradient. Various agents that promote cyclic AMP accumulation in intact lymphocytes were compared in their ability to stimulate adenylate cyclase activity in the individual fractions. Plasma-membrane-rich fractions that were essentially free of other subcellular particles as judged by electron microscopy and marker enzyme measurements responded to fluoride, but weakly or not at all to prostaglandin E1 and other prostaglandins. Microsomal and mitochondrial-rich fractions responded markedly to both prostaglandin E1 and fluoride. In some, but not all, experiments phytohaemagglutinin produced a modest increase in enzyme activity in plasma-membrane-rich fractions. Catecholamines, histamine, parathyrin, glucagon and corticotropin produced little or no response. In the absence of theophylline, adenosine (1-10 micronM) stimulated basal enzyme activity, although at higher concentrations the responses to prostaglandin E1 and fluoride were inhibited. GTP (1-100 micronM) and GMP(5-1000 micronM) respectively inhibited or stimulated the response to fluoride, whereas the converse was true with prostaglandin E1.
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PMID:Adenylate cyclase activity in lymphocyte subcellular fractions. Characterization of non-nuclear adenylate cyclase. 19 77

The delta6 desaturation of unsaturated acyl-CoA is the first reaction involved in the normal biosynthesis of all polyunsaturated fatty acids families in animal microsomes. Due to this key position it can regulate the biosynthesis of the fatty acids of the series. The reaction is modified by competition with substrates and products, ATP, and acyl-CoA acceptors. Dietary glucose and fructose inhibit the enzyme whereas protein diets and essential fatty acid deficient diets enhance the reaction independently of hormonal effects. The enzyme is sensitive to hormones concentration. Insulin enhance the reaction but the effect is eliminated by protein synthesis inhibition. Hyperglucemic hormones as glucagon, and epinephrine depress the activity of the delta6 desaturase by reactions triggers by an increase of cAMP concentration. The lateral relation of linoleic or alpha-linolenic microsomal elongation is insensitive to insulin, glucagon, epinephrine and protein. All these effects have been proved by either in vivo experiments or cell culture using linoleic or alpha-linolenic acids as substrates.
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PMID:Regulatory function of delta6 desaturate -- key enzyme of polyunsaturated fatty acid synthesis. 20 Jan 15

1. The subcellular distribution and maturation of Ruthenium Red-insensitive Ca(2+) transport activity were determined in livers of rats ranging in age from 3 days pre-term to 10 weeks of adult life and compared with those of glucose 6-phosphatase, 5'-nucleotidase and Ruthenium Red-sensitive Ca(2+) transport. Initial rates of Ruthenium Red-insensitive Ca(2+) transport were highest in those fractions enriched in glucose 6-phosphatase, i.e. the microsomal fraction; this fraction was devoid of Ruthenium Red-sensitive Ca(2+) transport activity. Although the heaviest fraction (nuclear) contained significant amounts of 5'-nucleotidase activity it was devoid of Ruthenium Red-insensitive Ca(2+) transport activity. 2. Foetal rat liver contain minimal amounts of Ruthenium Red-insensitive Ca(2+) transport activity, glucose 6-phosphatase and 5'-nucleotidase activities. These begin to be expressed concomitantly soon after birth; Ruthenium Red-insensitive Ca(2+) transport is maximal by 3 to 4 days and remains so for up to at least 10 weeks of adult life. Glucose 6-phosphatase also reaches a peak at 3-4 days, but then rapidly decreases to approach adult values. Maximal activity of 5'-nucleotidase in the microsomal and nuclear fractions is seen about 4-6 days after birth; this enzyme activity remains increased for up to about 10 days and then falls, but not as rapidly as glucose 6-phosphatase. It is tentatively suggested that the bulk of the Ruthenium Red-insensitive Ca(2+) transport is attributable to the system derived from the endoplasmic reticulum. 3. Administration of glucagon to adult rats enhances by 2-3-fold the initial rate of Ruthenium Red-insensitive Ca(2+) transport in the intermediate but not the microsomal fraction. The hormone-induced effect is fully suppressed by co-administration of puromycin, is dose-dependent with half-maximal response at approx. 1mug of glucagon/100g body wt. and time-dependent exhibiting a half-maximal response about 1h after administration of the hormone. 4. Ruthenium Red-insensitive Ca(2+) transport in the post-mitochondrial fraction of foetal liver also responds to the administration in situ of glucagon. The response, which also is prevented by co-administration of puromycin, is maximal in those foetuses nearing term. The suggestion is made that these effects of the hormone on Ruthenium Red-insensitive Ca(2+) transport are an integral part of the physiological network in the liver cell.
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PMID:The subcellular location, maturation and response to increased plasma glucagon of ruthenium red-insensitive calcium-ion transport in rat liver. 21 18

Anglerfish islets were homogenized in 0.25 M sucrose and separated into seven separate subcellular fractions by differential and discontinuous density gradient centrifugation. The objective was to isolate microsomes and secretory granules in a highly purified state. The fractions were characterized by electron microscopy and chemical analyses. Each fraction was assayed for its content of protein, RNA, DNA, immunoreactive insulin (IRI), and immunoreactive glucagon (IRG). Ultrastructural examination showed that two of the seven subcellular fractions contain primarily mitochondria, and that two others consist almost exclusively of secretory granules. A fifth fraction contains rough and smooth microsomal vesicles. The remaining two fractions are the cell supernate and the nuclei and cell debris. The content of DNA and RNA in all fractions is consistent with the observed ultrastructure. More than 82 percent of the total cellular IRI and 89(percent) of the total cellular IRG are found in the fractions of secretory granules. The combined fractions of secretory granules and microsomes consistently yield >93 percent of the total IRG. These results indicate that the fractionation procedure employed yields fractions of microsomes and secretory granules that contain nearly all the immunoassayable insulin and glucagons found in whole islet tissue. These fractions are thus considered suitable for study of proinsulin and proglucagon biosynthesis and their metabolic conversion at the subcellular level.
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PMID:Studies on proinsulin and proglucagon biosynthesis and conversion at the subcellular level. I. Fractionation procedure and characterization of the subcellular fractions. 32 17

The irreversible reaction between liver esterases and the active-site-directed inhibitor bis(4-nitrophenyl)phosphate can be used in vivo both for the estimation of the esterase contents and for the measurement of the esterase degradation rates. A method based on this reaction is described which allows the simultaneous estimation of the rate constants of degradation and synthesis of esterases during a period of change in protein concentration. Rat liver was found to contain about 1 mg of organophosphate-binding esterases per g of fresh tissue while the microsomal fraction contains about 30 mg of esterases per g of microsomal protein. Esterase degradation and de novo synthesis were shown to remain in equilibrium for a period of at least five days following the injection of 10 mg bis(4-nitro-[14C]phenyl)phosphate per kg. The decrease of the relative amount of labeled esterases with time was found to follow first-order kinetics yielding an average esterase degrading constant of 0.0165 h-1 which corresponds to a half-life of 42 h. These data were confirmed by an independent experiment using one of the standard procedures for the estimation of degradation rates: [14C]leucine was incorporated and one of the esterases was subsequently isolated by immuno-precipitation. Using isoelectric focussing and dodecyl sulfate electrophoretic methods, the various esterase isoenzymes appeared to have very similar, if not identical turnover rates. This method for the estimation of the turnover characteristics was applied to evaluate hormone effects on liver esterases. The time course of the contents and the turnover of liver esterases was measured under the influence of glucagon treatment in diabetic rats and under the influence of high doses of insulin. The esterase content decreased faster than the average content of microsomal protein under the influence of glucagon. The reverse effect was observed with insulin-treated rats. Both insulin and glucagon apparently reduced the intracellular esterase turnover in rat liver. Kinetic analysis of the results revealed that insulin mainly lowered the esterase degradation rate, though the rate of esterase synthesis might also have been restricted. In the glucagon-treated rats the de novo synthesis of esterases was strongly reduced.
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PMID:A method for the estimation of esterase synthesis and degradation and its application to evaluate the influence of insulin and glucagon. 39 10

An insulin radioreceptor assay (RRA) using human placental microsomal membranes was used to measure insulin-like activity (ILA) extracted from human plasma concentrates (Cohn fraction IV-4) by acid ethanol. The soluble activity (ILAs), chromatographed on Sephadex G-75 in 1 M acetic acid, migrated as a small molecule (fractional elution volume, 0.56) ahead of insulin (fractional elution volume, 0.70), whereas at neutral pH, ILAs migrated as a large molecular weight species. The ILAs peak from acid gel filtration on Sephadex was further purified by chromatography on carboxymethyl cellulose (CMC). The ILAs peak from both Sephadex and CMC diluted parallel to the porcine insulin standard in the insulin RRA and was totally unreactive in an insulin RIA. The CMC-purified material was iodinated and purified by binding to and elution from human placental membranes. The binding of [125I]ILAs to human placental membranes was inhibited only minimally by insulin and proinsulin and not at all by epidermal growth factor, nerve growth factor, glucagon, or lactogenic hormones, including human growth hormone. Multiplication-stimulating activity (MSA) inhibited in a manner parallel to ILAs. A Scatchard plot of the binding data was nonlinear. Sephadex ILAs was subjected to isoelectric focusing. The fractions assayed in both insulin and ILAs RRAs yielded comparable results. Peaks of ILA were observed at pHs 5.3, 6.6, and 8.4. When CMC-ILA was subjected to isoelectric focusing in polyacrylamide, a single peak of activity migrating between pH 6.2-6.8 was seen. [125I]ILAs focused at exactly the same pH. Electrophoresis of CMC-ILAs in acid-urea revealed a sharp peak of activity migrating with one of the five protein bands seen after staining. Again, [125I]ILAs comigrated with unlabeled ILAs. The molecular weight of ILAs, as determined on a calibrated Sephadex G-150 column at neutral pH, was 9,000-10,000 daltons. CMC-ILAs stimulated [14C]glucose incorporation into triglycerides of rat adipose tissue and augmented [3H]thymidine incorporation into human fibroblasts, chicken embryo fibroblasts, and BALB 3T3 cells as well as [35S]sulfate incorporation into macromolecules of rabbit chondrocyte culture medium. In summary, ILAs isolated on the basis of a RRA for insulin is a slightly acidic peptide with some of the biological activities expected of a somatomedin.
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PMID:Partial purification, characterization, and assay of a slightly acidic insulin-like peptide (ILAs) from human plasma. 40 Jul 41

It is now well established that insulin biosynthesis proceeds through a precursor molecule, proinsulin. This single polypeptide chain form has been identified as a ribosomal product in the microsomal fraction from islet tissues. The newly synthesized peptide chain, after folding and thiol oxidation, is transferred to the Golgi apparatus where it begins to undergo proteolytic processing to insulin and packaging into secretory granules. The secretion from the cells of significant amounts of newly synthesized material by exocytosis begins only one hour or more after biosynthesis and this process is regulated by several factors, including glucose. Foci of current attention discussed in this paper include (1) the possible existence of larger precursor forms than proinsulin, especially short-lived biosynthetic transients with extended NH2-termini analogous to the recently described immunoglobulin L chain and proparathyroid hormone precursors; (2) the large-scale production of insulin by chemical or genetic engineering approaches; (3) isolation of beta-cell plasma membranes; (4) regulatory mechanisms for the biosynthesis and secretion of insulin, the possible role of mRNA modification in this process, and effects of somatostatin on insulin biosynthesis and secretion; (5) studies on the secretion, metabolism and clinical usefulness of the proinsulin C-peptide; (6) finally, the biosynthesis of glucagon and other peptide hormones and the general significance of precursor forms.
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PMID:Biosynthesis of insulin and glucagon: a view of the current state of the art. 78 79


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