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 need for chaotropic eluents in immunoaffinity chromatography is a consequence of the high affinities of antibodies towards their antigens. This affinity is decreased and elution of antiglucagon antibodies from a column of immobilized glucagon can be achieved under mild conditions when the steric complementarity to the antibody binding site is perturbed by selective chemical modification of the hormone. The effects of reaction with 2-hydroxy-5-nitrobenzyl bromide, tetranitromethane and hydrogen peroxide have been studied. Conversely, treatment of immobilized antibodies with 2-hydroxy-5-nitrobenzyl bromide facilitates the elution of glucagon during immunoaffinity chromatography. The general implications of these results are discussed.
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PMID:Avoidance of strongly chaotropic eluents for immunoaffinity chromatography by chemical modification of immobilized ligand. 0 98

The binding and action of glucagon at its receptor in hepatic plasma membranes have been compared, as a function of pH, with that of glucagon containing iodotyrosyl residues. Iodinated glucagon, at pH 7.0 and below, binds to the receptor and activates adenylate cyclase with an affinity about threefold higher than that of native glucagon. At pH 8.5, the affinity of the receptor for native glucagon is the same as that seen at pH 7.0. However, iodinated glucagon binds with a lowered affinity with increasing pH. The decreased affinity of the iodinated hormone correlates with ionization of the iodotyrosyl phenoxy groups, which has a pKa of 8.2. It is suggested that the decreased affinity is actually due to the inability of the ionized iodoglucagon to bind to the receptor. The relative potency of native and iodoglucagon will depend, therefore, on the concentrations of ionized and un-ionized species of iodoglucagon, which in turn depend on the pH of the medium. We conclude that incorporation of iodine atoms in the tyrosyl residues of glucagon has two major effects: (i) the iodine atom increases hydrophobic interaction of the hormone with the receptor and (ii) ionization of the phenoxy groups results in the loss of biological activity possibly as the result of loss of hydrogen bonding capability. Thus, the tyrosyl residues in glucagon are critically involved in the function of the hormone.
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PMID:Effects of iodination of tyrosyl residues on the binding and action of glucagon at its receptor. 0 75

It is proposed that glucagon, a polypeptide hormone, is delicately balanced between two major conformational states. Utilizing a new predictive model [Chou, P.Y., and Fasman, G.D. (1974), Biochemistry 13, 222] which considers all the conformational states in proteins (helix, beta sheet, random coil, and beta turns), the secondary structural regions of glucagon are computed herein. The conformational sensitivity of glucagon may be due to residues 19-27 which have both alpha-helical potential (mean value of Palpha = 1.19) as well as beta-sheet potential (mean value of Pbeta = 1.25). Two conformational states are predicted for glucagon. In predicted form (a), residues 5-10 form a beta-sheet region while residues 19-27 form an alpha-helical region (31% alpha, 21% beta) agreeing well with the circular dichroism (CD) spectra of glucagon. The similarity in the CD spectra of glucagon and insulin further suggests the presence of beta structure in glucagon, since X-ray analysis of insulin showed 24% beta sheet. In predicted form (b), both regions, residues 5-10 and residues 19-27, are beta sheets sheets (0% alpha, 52% beta) in agreement with the infrared spectral evidence that glucagon gels and fibrils have a predominant beta-sheet conformation. Since three reverse beta turns are predicted at residues 2-5, 10-13, and 15-18, glucagon may possess tertiary structure in agreement with viscosity and tritium-hydrogen exchange experiments. A proposal is offered concerning an induced alpha yields beta transition at residues 22-27 in glucagon during receptor site binding. Amino acid substitutions are proposed which should disrupt the beta sheets of glucagon with concomitant loss of biological activity. The experimental findings that glucagon aggregates to form dimers, trimers, and hexamers can be explained in terms of beta-sheet interactions as outlined in the present predictive model. Thus the conflicting conclusions of previous workers, concerning the conformation of glucagon in different environments, can be rationalized by the suggested conformational transition occurring within the molecule.
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PMID:The conformation of glucagon: predictions and consequences. 113 71

Looking back at the experiences of our own and of others in the past decade or so on the total synthesis of proteins and polypeptides, we have analyzed the inherent contradictions of the two alternative methods of synthesis on the basis of the dialectical viewpoint of "one dividing into two". Either the solid or the liquid-phase synthesis is fraught with difficulties when the target exceeds 100 amino acid residues. A new synthetic strategy has been developed which we believe can resolve the contradictions inherent in the synthesis of larger peptides--the solid phase stepwise condensation of peptide fragments instead of amino acids. Following repeated practice guided by the spirit of independence and self-reliance, we have succeeded in synthesizing first of all a new supporting resin layer which provisionally meets our requirements. We shall describe in the present paper the successful total synthesis of the nonacosapeptide glucagon using this supporting resin layer. Four peptide fragments (5, 6, 9, 6), synthesized with the aid of classical methods, have been coupled stepwise to a resin-bound tripeptide, with an efficiency of over 95% for each step. After treatment with hydrogen fluoride and purification twice by means of column chromatography, rhombic dodecahedral crystals of glucagon have obtained which are identical with natural products in respect of amino acid compositions, chromatographic and disc-electrophoretic behaviour, etc. The overall yield is about 17%. In view of the characteristic abundance in glucagon of various kinds of functional groups which form unfavourable obstacles to the course of synthesis, this relatively high yield and the ease with which crystalline products can be obtained testify to the potential of the new technique in the eventual total synthesis of larger proteins.
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PMID:Total synthesis of crystalline glucagon by the method of solid phase condensation of fragments. Protein Synthesis Group, Shanghai Institute of Biochemistry, Academia Sinica. 122 98

The structure of monomeric glucagon in dilute aqueous solution was studied by 500 MHz NMR. Hydrogen-deuterium exchange experiments monitored by NMR showed that the backbone amide NHs form intrastrand hydrogen bonds suggesting the existence of some degree of compact structure. The temperature dependent shift of several amide NH resonances supported the above conclusion. The small J coupling constants arising from the interactions between 6 amide NHs and C alpha Hs (less than 6 Hz) imply a helical structure.
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PMID:The conformation of glucagon in dilute aqueous solution as studied by 1H NMR. 133 83

Patients with liver cirrhosis develop marked abnormalities in small bowel motility and high plasma glucagon levels. Disturbances in small intestinal motor activity could be related to hyperglucagonemia. To investigate the relationship between fasting plasma glucagon levels and changes in small bowel motility in patients with liver cirrhosis, eighteen cirrhotic patients and ten controls were studied. Plasma glucagon was measured by RIA. Mouth to cecum transit time was estimated by lactulose hydrogen breath test. Fasting small bowel motility was investigated by means of intraluminal manometry. Plasma glucagon levels were significantly higher in patients with cirrhosis (61 +/- 5 pmol/l) than in controls (32 +/- 3 pmol/l); p < 0.01. In patients with liver disease, plasma glucagon levels were not significantly correlated to mouth to cecum transit time (r: -0.32), duration of migrating motor complex (r: -0.24), nor to the frequency of multiple clustered contractions (r: -0.26). The degree of small bowel dysmotility is not related to plasma glucagon levels in patients with hepatic cirrhosis. These results do not support the hypothesis that hyperglucagonemia plays an important pathogenic role in the abnormalities of gut motility in cirrhosis.
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PMID:[Are disturbances of small intestinal motility associated with hyperglucagonemia in patients with liver cirrhosis?]. 134 Sep 93

Effects of various forms of gastric surgery on gut hormones and pancreatic secretions were examined using canine models. These operative procedures included simple laparotomy (group A; n = 13), truncal vagotomy with pyloroplasty (B; n = 17), selective proximal vagotomy (C; n = 17), proximal gastrectomy with pyloroplasty (D; n = 6), proximal gastrectomy with truncal vagotomy and pyloroplasty (E; n = 7), and distal gastrectomy (F; n = 19). The mean fasting serum gastrin and secretin levels (pg/ml) were 71.0, 82.5 in A, 94.0, 97.7 in B, 62.1, 108.1 in C, 58.2, 123.0 in D, 91.2, 138.6 in E, and 50.9, 74.5 in F, respectively. The mean value of plasma pancreatic glucagon (pg/ml) showed 73.6, 109.9, 106.8, 47.2, 37.8, and 74.5 in each of the six groups. Significant correlations were observed between values of serum lipase and those of serum gastrin as well as between the amount of pancreatic secretions and serum secretin levels. Pancreatic secretions were decreased markedly in group F and moderately in B. Basal tissue blood flow measured by hydrogen clearance method was low in D, E, and F when compared with that in A.
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PMID:[Effects of various forms of gastric surgery on gut hormones and pancreatic secretions]. 194 82

In this study, the author intended to examine the validity of the inhaled hydrogen gas clearance method (i-H2) for determination of the hepatic blood flow (HBF), and also to show some applicabilities of the method in experimental animals and patients with liver diseases. Simultaneous determinations of HBF by i-H2 and electromagnetic flowmetry in rabbits revealed an excellent correlation between the values obtained by the two methods. Moreover, HBF in rabbits measured by i-H2 varied in parallel with that by thermocouple flowmetry or laser Doppler velocimetry after administration of norepinephrine, propranolol or glucagon. In carbon tetrachloride-treated rats, HBF measured by i-H2 correlated better with the severity of damage in the sinusoidal structure than the severity of hepatic cell injury or the serum levels of transaminases. HBF as determined by i-H2 was significantly decreased in acute hepatitis (AH), chronic inactive hepatitis (CIH), chronic active hepatitis (CAH), liver cirrhosis (LC) and fatty liver. Reduced HBF in AH returned to normal during recovery of the disease. The ratio of HBF in tumor/normal tissue was greater than 1.0 for hepatocellular carcinoma in contrast to the ratio of less than 1.0 for metastatic liver carcinoma. Propranolol caused a decrease in HBF by 31%, and vasopressin by 39% in patients with CIH or LC. In contrast, glucagon induced its increase by 65%, 35% and 17%, respectively, in patients with CIH, AH and LC.
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PMID:[Measurement of hepatic blood flow by the hydrogen gas clearance method. Experimental and clinical observations]. 236 96

Disturbances of gastrointestinal motility are a common feature of diabetes mellitus and are usually ascribed to autonomic neuropathy. In order to assess the role of other factors on changes in motility in diabetes we have studied the stomach to caecum transit time (SCTT) during the progression of streptozotocin induced diabetes in the rat. Rats were used one, two, four, and eight weeks after a single injection of streptozotocin and age matched animals were used as controls. In further experiments non-diabetic rats received a bolus injection of pancreatic glucagon (50 or 75 micrograms intraperitoneally) or its diluent. SCTT was estimated using the non-invasive hydrogen excretion method. SCTT was unaffected by the age of the animal (mean (SEM) value: 101 (5) min), but was significantly delayed at one week (139 (11) min, p less than 0.01), two weeks (163 (16) min, p less than 0.01), four weeks (148 (9) min, p less than 0.01), and eight weeks (171 (13) min, p less than 0.01) after streptozotocin. SCTT was also slower during hyperglucagonaemia (control 96 (6) min; glucagon treated 50 micrograms: 120 (7) min, p less than 0.05 and 75 micrograms: 127 (8), p less than 0.05). Since autonomic neuropathy is not a recognised feature of the initial stages of diabetes hyperglucagonaemia may be responsible, at least in part, for diabetes induced changes in gastrointestinal motility.
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PMID:Delayed stomach to caecum transit time in the diabetic rat. Possible role of hyperglucagonaemia. 237 69

In this preliminary study, we examined the effects of acarbose and placebo together with a standardized breakfast on blood glucose levels, on breath hydrogen excretion and on plasma insulin and glucagon levels; in addition, the effects on fasting blood levels of metabolites were studied following an evening meal with acarbose or placebo. Acarbose significantly reduced blood glucose levels in 10 patients with alcoholic cirrhosis following a meal containing 100 g of carbohydrate. There were no significant changes in plasma insulin after breakfast but glucagon levels were increased at 1 h after the meal. Breath hydrogen excretion did not change significantly. Acarbose given with a late evening snack reduced fasting beta-hydroxybutyrate levels the next morning in these cirrhotic patients.
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PMID:Effects of the glucosidase inhibitor acarbose in patients with liver cirrhosis. 251 58


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