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)

Several methods for tissue embedding in polyethylene glycol (PEG) were compared with regard to their applicability for pre-embedding immunoelectronmicroscopy. Existing embedding procedures gave unsatisfactory results and therefore a modified procedure was developed. This method, consisting of very brief tissue infiltration with PEG 1500, to which 3% water is added, allowed adequate tissue sectioning. Using these sections for preembedding immunoelectronmicroscopical localisation of glucagon in bovine pancreatic islets adequate ultrastructural morphology was obtained in combination with excellent preservation of peptide hormone immunoreactivity.
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PMID:Polyethylene glycol embedded tissue sections for immunoelectronmicroscopy. 703 6

Insulin antibodies (IA) are detectable in the sera of most insulin-treated patients with diabetes mellitus. Antibodies to exogenous insulin sometimes cause clinical symptoms of insulin resistance, allergy, and local lipoatrophy. Although the frequency of these complications has diminished with the use of highly purified porcine insulin or recombinant human insulin, there are some patients with high titer of IA. Autoantibodies to insulin (IAA) are also described. IAA has been reported to be in association with both insulin-dependent diabetes mellitus (IDDM) and polyendocrine autoimmune disease. For many years these antibodies have been measured by radiobinding assay (RBA) in which the complexes are precipitated non-specifically by polyethylene glycol. In the present study we developed a rapid and quantitative enzyme-linked immunosorbent assay (ELISA) method for measuring IA and IAA using recombinant human insulin antigen. We applied this method to the samples obtained from patients with diabetes mellitus and autoimmune thyroid disease and then compared the results with those obtained from the RBA method. The calibration curve for ELISA was derived from the dilution curve of a single serum from a patient positive for insulin antibody, and the results were expressed arbitrarily as ELISA UNIT. The calibration curve was approximately linear on the log-log scale within the range of 0.1-2.0 at optical density (OD)450nm, (6.25-200 ELISA UNIT). The intra-assay (CV = 2.3-3.1%) and inter-assay (CV = 2.8-7.2%) precisions were acceptable. Recovery rate varied from 74.5% to 118.5% and dilution experiments showed good linearity. Specificity was demonstrated by substituting purified human IgG for the test serum and glucagon for insulin. Except for hemoglobin, coexisting substances in serum had almost no effect on ELISA. The range of ELISA UNIT (Mean +/- SD) of 83 normal sera was 12.7 +/- 4.6. Positivity for IA by ELISA (> normal Mean + 3SD) was 11 out of 58 (19.0%) and 26 out of 55 (47.3%) in patients with IDDM and with non-insulin-dependent diabetes mellitus (NIDDM) who were treated with insulin, respectively. Positivity for IAA by ELISA was 5 out of 173 (2.8%) and 1 out of 20 (5.0%) in patients with NIDDM without insulin therapy and hyperthyroidism due to Graves' disease, respectively. However, by RBA, we detected 4 other cases positive for IAA in NIDDM without insulin therapy and one case in Graves' disease. The present study demonstrates that the newly developed method of ELISA using recombinant human insulin antigen is clinically useful for measuring IA and IAA.
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PMID:[The measurement of insulin antibodies and insulin autoantibodies by enzyme-linked immunosorbent assay using recombinant human insulin antigen and its clinical application]. 795 8

In amphibian liver, signal transduction of [Arg8]vasotocin (AVT), a "classical" Ca(2+)-dependent hormone in rat liver, is mediated via the generation of adenosine 3',5'-cyclic monophosphate (cAMP) and not via inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. In isolated hepatocytes from axolotl, hormones that stimulated cAMP formation (the order of efficacy was glucagon > isoprenaline > epinephrine > or = AVT) also provoked a pronounced increase in cytosolic Ca2+, as indicated from changes in fura 2 fluorescence. 8-Bromoadenosine 3',5'-cyclic monophosphate at 100 microM was as potent as maximally effective concentrations of glucagon. Ins(1,4,5)P3 mobilized Ca2+ from the endoplasmic reticulum of saponin-permeabilized axolotl hepatocytes with a half-maximal effect at 0.65 microM, as did GTP (20 microM), even in the absence of polyethylene glycol. However, the hormonally induced increase in cytosolic Ca2+ was not due to a mobilization of the cation from internal stores by Ins(1,4,5)P3, but to an increased inflow from the extracellular medium. We conclude that in axolotl liver, in contrast to rat liver, hormones stimulate the production of cAMP that, in addition to stimulating processes such as glycogenolysis, also regulates the opening of an ion gate in the plasma membrane, which allows the inflow of Ca2+. To our knowledge this is the first demonstration of a second messenger-operated Ca2+ channel in a splanchnic tissue.
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PMID:Hormone-induced rise in cytosolic Ca2+ in axolotl hepatocytes: extracellular origin and control by cAMP. 823 80

The binding properties of hepatic aldolase (B) were determined in digitonin-permeabilized rat hepatocytes after the cells had been preincubated with either glycolytic or gluconeogenic substrates. In hepatocytes that had been preincubated in medium containing 5 mM glucose as sole carbohydrate substrate, binding of aldolase to the hepatocyte matrix was maximal at low KCl concentrations (20 mM) or bivalent cation concentrations (1 mM Mg2+) and half-maximal dissociation occurred at 50 mM KCl. Preincubation of hepatocytes (for 10-30 min) with glucose or mannose (10-40 mM), fructose, sorbitol, dihydroxyacetone or glycerol (1-10 mM), caused a leftward shift of the salt dissociation curve (maximum binding at 10 mM KCl; half-maximum dissociation at 35 mM KCl) but did not affect the proportion of bound enzyme at low or high KCl concentrations. Galactose and 2-deoxyglucose had no effect on aldolase binding. Inhibitors of glucokinase (mannoheptulose and glucosamine) suppressed the effects of glucose but not the effects of sorbitol, glycerol or dihydroxyacetone. Glucagon suppressed the effects of glucose, fructose and dihydroxyacetone but not glycerol. Poly(ethylene glycol) (PEG) (2-10%), added to the permeabilization medium, increased aldolase binding and caused a rightward shift in the salt dissociation curve. In the presence of PEG (6-8%), the effects of substrates on aldolase dissociation were shifted to higher salt concentrations (50-100 mM versus 35 mM KCl). The effects of substrates (added to the intact cell) on aldolase binding to the permeabilized cell could be mimicked by addition of the phosphorylated derivatives of these substrates to the permeabilized cell. Of the intermediates tested dihydroxyacetone phosphate and fructose 1,6-bisphosphate were the most effective at dissociating aldolase (A50 values of 20 microM and 40 microM respectively). Other effective intermediates in order of decreasing potency were fructose 1-phosphate, glycerol 3-phosphate, glucose 1,6-bisphosphate/fructose 2,6-bisphosphate. These results show that aldolase B binds to the hepatocyte matrix by a salt-dependent mechanism that is influenced by macromolecular crowding and metabolic intermediates. Maximum binding occurs when hepatocytes are incubated in the absence of glycolytic and gluconeogenic substrates and minimum binding occurs in the presence of substrates that are precursors of either fructose 1,6-bisphosphate or triose phosphates. Since the bound form of aldolase represents a kinetically less active state it is proposed that aldolase binding and dissociation may be a mechanism for buffering the concentrations of metabolic intermediates.
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PMID:Substrate modulation of aldolase B binding in hepatocytes. 861 43

Glucagon-like insulinotropic peptide (GLP-1) and its analogs are of interest because of their therapeutic potential in type II diabetes. LY315902 is a GLP-1-(7-37)-OH analog with a modified N-terminus (IP7), an octanoic acid (C8) acylated on the lysine residue at position 34, and a substitution with arginine at position 26. We developed a sensitive and specific radioimmunoassay (RIA) for the determination of immunoreactive LY315902 in the plasma of animals. A homobifunctional cross-linker was used to couple the nonacylated form of LY315902 [IP7-R26-GLP-1-(7-37)-OH] to carrier proteins to enhance its immunogenicity. Following immunization, animal antisera were screened by RIA for the presence of LY315902 antibodies. One rabbit produced a high-affinity antiserum that display insignificant cross-reactivity against two forms of native GLP-1 and possible major metabolites of LY315902. In this RIA method, plasma samples were combined with radioiodinated LY315902 and rabbit anti-IP7-R26-GLP-1-(7-37)-OH serum, and then incubated overnight at room temperature. The bound forms of LY315902 were separated by polyethylene glycol assisted second antibody precipitation. The sensitivity of the assay was estimated to be 19 pM. Inter-assay precision (%CV) and accuracy (recovery) for quality control samples in dog plasma ranged from 8.0% to 14.7% and 92.8% to 107.3%, respectively. By applying this assay to measure plasma concentrations of immunoreactive LY315902 in dogs following twice daily subcutaneous injections of LY315902, we determined that the plasma half-life of LY315902 is significantly longer than that of native GLP-1-(7-37)-OH. We concluded that the structural modifications which were made to produce LY315902 prolonged its plasma half-life. The extended plasma half-life of LY315902 correlated well with its prolonged pharmacology in dogs.
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PMID:A radioimmunoassay for LY315902, an analog of glucagon-like insulinotropic peptide, and its application in the study of canine pharmacokinetics. 923 14

To date, glucagon-like peptide 1(7-36) amide (tGLP-1) has been found to affect the neurohypophysial and cardiovascular functions in normotensive and normovolaemic rats. The aim of the present study was to investigate possible effects of tGLP-1 on the mean arterial blood pressure and the release of vasopressin and oxytocin under conditions of blood volume depletion in the rat. In the first series of experiments, the animals were injected i.p. with either 0.15 M saline or 30% polyethylene glycol (PEG). PEG caused an 18% reduction of blood volume 1 h after injection. No significant changes in the mean arterial blood pressure were found in either normo- or hypovolaemic rats during the experiment. tGLP-1 injected i.c.v. at a dose of 1 microg/5 microl 1 h after the i.p. injection increased similarly the arterial blood pressure in normo- and hypovolaemic rats. The plasma vasopressin/oxytocin concentrations were markedly elevated in hypovolaemic animals and tGLP-1 further augmented the release of both hormones. In the second study, hypovolaemia was induced by double blood withdrawal. The haemorrhage resulted in a marked decrease of the mean arterial blood pressure and in the elevated plasma vasopressin/oxytocin concentrations. tGLP-1 injected immediately after the second blood withdrawal increased the arterial blood pressure. In parallel, tGLP-1 enhanced significantly vasopressin and oxytocin secretion when compared with haemorrhaged, saline-injected rats. The results of this study indicate that tGLP-1 may affect the arterial blood pressure and the secretion of neurohypophysial hormones under pathological conditions brought about by blood volume depletion.
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PMID:Effects of glucagon-like peptide-1(7-36) amide on neurohypophysial and cardiovascular functions under hypo- or normotensive hypovolaemia in the rat. 1183 48

CT colonography is likely to play an important role in colorectal cancer screening. The ability of this new technique to detect colorectal polyps and cancer is predicated on an optimally cleansed and distended colon. Whereas the most common reported colonic cleansing regimen employed for CT colonography is polyethylene glycol lavage solution, saline cathartics such as sodium phosphate and magnesium citrate offer the advantage of a drier cleansed colon. Positive labeling of residual stool and fluid combined with electronic substraction of tagged material is under investigation. This new technique would eliminate purgative bowel cleansing and increase patient acceptance of CT colonography. Colonic distention is easily and reliably achieved with atmospheric air, although carbon dioxide is being evaluated as a more comfortable alternative. The use of antispasmodics for CT colonography is controversial. Glucagon is no longer used at centers where a clear benefit has not been found. Intravenous contrast may be useful in a specific subset of patients undergoing CT colonography, although it is doubtful that it will be used routinely for CT colonography.
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PMID:CT colonography: examination prerequisites. 1217 54

Interference in radioimmunoassays (RIAs) was frequently encountered during endocrinological studies of the emu (Dromaius novaehollandiae). Interference was greatest when serum was cloudy or opaque. Such samples appeared seasonally, in spring and summer during the phase of fat deposition, and in the winter when females were laying. These poor quality samples did not allow accurate measurement by RIAs of several peptide hormones for a full year. To prepare them for assay, these sera were clarified using a polyethylene glycol (PEG) solution at a final concentration of 7.5%. This treatment was effective in most cases. After treatment with the PEG, recoveries of LH, glucagon, and prolactin were greater than 75% and that for insulin was 40%. Regardless of the level of recovery, there was a high correlation of assay results between non-opaque native and PEG-treated sera. Serum samples containing large amounts of interfering high molecular weight components, such as lipoproteins, can be clarified with PEG, enabling their accurate measurement by RIA.
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PMID:Clarification of emu serum for peptide hormone assay using polyethylene glycol precipitation. 1281 80

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, adalimumab, alefacept, alemtuzumab, almotriptan, AMGN-0007, anakinra, anti-CTLA-4 Mab, L-arginine hydrochloride, arzoxifene hydrochloride, astemizole, atazanavir sulfate, atlizumab; Belimumab, BG-9928, binodenoson, bosentan, botulinum toxin type B, bovine lactoferrin, BufferGel; Caspofungin acetate, ciclesonide,cilomilast, ciluprevir, clofarabine, CVT-3146; Darbepoetin alfa, desloratadine, diflomotecan, doripenem, dronedarone hydrochloride, drotrecogin alfa (activated), DT388-GM-CSF, duloxetine hydrochloride, E-5564, efalizumab, enfuvirtide, esomeprazole magnesium, estradiol acetate, ETC-642, exenatide, exisulind, ezetimib; Febuxostat; Gallium maltolate, ganirelix acetate, garenoxacin mesilate, gefitinib; H11, HuMax; IL-15, IDD-1, IGIV-C, imatinib mesylate, ISIS-14803, ITF-1697, ivabradine hydrochloride; KRN-5500; L-365260, levetiracetam, levosimendan, licofelone, linezolid, LJP-1082, lopinavir lumiracoxib; MCC-478, melatonin, morphine hydrochloride, morphine-6-glucuronide, moxidectin; N-Acetylcarnosine, natalizumab, NM-702, NNC-05-1869, NSC-703940; Ocinaplon OM-89, omalizumab, omeprazole/ sodium bicarbonate, OPC-28326, ospemifene; PEG-filgrastim peginterferon alfa-2a, pegsunercept, pirfenidone, pralmorelin, pregabalin; Recombinant glucagon-like peptide-1 (7-36) amide, repifermin, RSD-1235; S-8184, selodenoson, sodium dichloroacetate, suberanilohydroxamic acid; TAS-102, terfenadine, teriparatide, tipranavir troxacitabine; Ximelagatran; YM-337.
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PMID:Gateways to clinical trials. 1473 33

OXY-1a is an extended-spectrum beta-lactamase from the conditional pathogenic bacterium Klebsiella oxytoca. OXY-1a is responsible for the antibiotic resistance of this pathogen. A soluble form of OXY-1a with a His tag at its C-terminus was overexpressed in Escherichia coli. The recombinant protein was purified and crystallized at room temperature using PEG 4000 as the main precipitant. Two crystal forms were obtained from the same growth conditions. One was orthorhombic, with crystals that diffracted to better than 1.9 A, while the other was tetragonal, with crystals that only diffracted to about 3.0 A. Complete data sets were collected from both crystal forms. The orthorhombic crystal belongs to space group P2(1)2(1)2(1), with unit-cell parameters a = 46.54, b = 73.43, c = 84.56 A, while the tetragonal crystal has unit-cell parameters a = b = 73.72, c = 96.81 A. The asymmetric unit of the orthorhombic crystal is estimated to contain one OXY-1a molecule, giving a crystal volume per protein weight (V(M)) of 2.25 A(3) Da(-1) and a solvent content of 45%.
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PMID:Expression, purification and crystallization of an extended-spectrum beta-lactamase from Klebsiella oxytoca. 1474 13


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