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 binding and degradation of insulin and glucagon to kidney cell membranes was examined. Time- and temperature-dependent specific binding of [125I]iodo-insulin to kidney cell membranes was demonstrated. The membranes also degraded insulin in a time-, temperature-, and protein concentration-dependent manner. The apparent Km of the degradation was 2.7 x 10(-7) M. Glucagon degradation by the kidney membranes was extremely active. Per milligram of protein the kidney membrane was over 20 times as active as the liver membrane. Even at 4 C, significant glucagon degradation occurred. Because of this very active degradation, glucagon binding could not be accurately assessed. The kidney glucagon-degrading activity was inhibited by glutahione and EDTA but unaffected by N-ethylmaleimide, ACTH, or insulin, all potent inhibitors of liver glucagon degradation. The apparent Km for glucagon degradation by the kidney, however, was essentially identical with that for the liver, 2.4 x 10(-6) M.
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PMID:Insulin and glucagon binding and degradation by kidney cell membranes. 10 82

Homogenate preparations of pancreatic islets have been found to degrade insulin by cleavage of the interchain disulfide bonds, followed by proteolysis of the resulting A and B chains. A proteolytic system of the pancreatic islets splitting not only 125I-labeled insulin A chain but also 125I-labeled glucagon at pH 7.0, was shown to be activated by glutathione and inhibited by EDTA. The results suggest that pancreatic islets contain both the thiol-protein disulfide oxidoreductase (glutathione : protein-disulfide oxidoreductase, EC 1.8.4.2) and the A and B chain-degrading enzyme(s). The effects of EDTA argue against the implication of cathepsins in insulin breakdown under the experimental conditions employed.
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PMID:Demonstration of insulin degradation by thiol-protein disulfide oxidoreductase (glutathione-insulin transhydrogenase) and proteinases of pancreatic islets. 17 41

Infusion of 2 MRC/kg X h calcitonin in anaesthetised dogs produced a significant increase in plasma-renin activity, clearance of 51Dr-EDTA and 125I-o-iodohipuric acid, heart rate and urinary excretion of sodium, potassium, calcium and phosphates, while serum electrolytes and mean arterial pressure markedly fell. Infusion of 5 mug/kg X min glucagon produced a significant fall of plasma-renin, heart rate rose, but arterial mean pressure fell, and serum and urinary electrolytes did not change significantly, Cyclic AMP (dibutyryl-cAMP) significantly stimulated renin at a dose of 5 mg/min, while there were no significant changes in blood pressure, heart rate and serum and urinary electrolytes.
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PMID:[The effects of calcitonin, glucagon and the dibutyryl derivative of cyclic AMP on plasma-renin activity (author's transl)]. 18 47

Treatment of rat liver plasma membranes with various commercial preparations of crude collagenase from Clostridium histolyticum at concentrations as low as 1 mug/ml, resulted in activation of the adenylate cyclase system. Maximal activation occurred at 50 to 100 mug/ml of collagenase, and promoted a 2- to 3-fold increase in the basal activity as well as in the activities stimulated by catecholamines, glucagon, fluoride, or GTP. This was due to an increase in the maximal velocity of the cyclizing reaction without any increase in the affinity of the enzyme for its substrate. Treatment of plasma membranes with crude collagenase did not induce gross structural modifications as judged by electron microscopic examination. 5'-Nucleotidase activity was slightly inhibited and ATPase activity remained unaffected. The stimulatory substance was nondialyzable, thermolabile, and inhibited by both EDTA and -SH reagents, thus appearing to be a protein. The following observations suggest the effects observed were due to other protease(s) present in crude collagenase: (a) only crude collagenase was active on liver adenylate cyclase: treatment with purified collagenase from C. histolyticum or from Achromobacter iophagus gave no stimulation; (b) the stimulatory activity was irreversible since washing of the membranes after treatment was without effect; (c) crude collagenase contained no lecithinase or sphingomyelinase activity under our conditions of adenylate cyclase assay; (d) after chromatography on Sephadex G-100, the activator appeared as a peak in the 30,000-dalton region and was clearly separated from the collagenase and clostripain peaks, but coincident with elastolytic and caseinolytic activities; (e) the effect of crude collagenase could be prevented by addition of elastin in vitro and was mimicked by purified elastase from hog pancreas. It remains to be seen whether the effects observed result from an increase in the catalytic constant of adenylate cyclase, or an unmasking of new catalytic sites.
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PMID:Proteolytic activation of rat liver adenylate cyclase by a contaminant of crude collagenase from Clostridium histolyticum. 19 49

In normal fed rats, glycogen synthase D phosphatase activity in a glycogen pellet preparation was only partially inhibited (approximately 50%) by high concentrations of EDTA. However, the proportion of phosphatase activity inhibited by EDTA was markedly and rapidly (15 s) increased following glucagon or cAMP administration. Epinephrine administration did not alter the proportion of activity inhibited by EDTA. Glucose administration rapidly (2 min) reduced the proportion of synthase phosphatase activity inhibitable by EDTA. That is, the effect of glucose was just the opposite of that produced by glucagon or cAMP. Insulin administration had no effect on phosphatase activity. Synthase phosphatase activity assayed in the absence of EDTA was similar in all groups except for a moderate increase after glucose administration. Addition of Mg2+ completely reversed EDTA inhibition. Phosphorylase phosphatase activity in each group was not modified by addition of EDTA, although the percentage of phosphorylase in the alpha form was higher in glucagon-treated and lower in the glucose-treated animals as expected. These data suggest the presence of rapidly interconvertible forms of either synthase phosphatase or its substrate synthase D, detectable as a change in EDTA inhibitability and subject to glucose and glucagon control.
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PMID:In vivo glucose-, glucagon-, and cAMP-induced changes in liver glycogen synthase phosphatase activity. 20 88

The reaction products of plasma enzyme degradation of TRH were identified by thin layer chromatography. The enzyme in normal rat plasma yields proline and pGlu-His as major reaction products. High concentrations of proline decrease peptide cleavage, resulting in greater amounts of acid TRH. The apparent Km of the enzyme is 4.1 X 10(-6) M. LHRH and neurotensin are competitive inhibitors with Ki of 5 X 10(-6) M and 1.5 X 10(-5) M, respectively. Somatostatin, MIF, oxytocin, arg-vasopressin, arg-vasotocin, neurophysin II and glucagon do not compete; and pGlu-His-Pro-OH, Glu-His-Pro-OH, pGlu-His, His-Pro-NH2, and Pro-NH2 do not affect enzyme activity. These data suggest that the substrated requires pGlu and a terminal or internal amide to complex with the enzyme. The enzyme is markedly inhibited by Cu++, Bal, benzamadine, p-(chloromercuri)-benzoic acid, moderately affected by EDTA and puromycin, and unaffected by mercaptoethanol. TSH does not affect enzyme activity while LH inhibits it moderately at high concentrations (300-600 pg/ml).
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PMID:Characteristics of the plasma TRH-degrading enzyme. 81 19

Unidirectional K+ fluxes were measured in suspensions of isolated rat liver parenchymal cells incubated with 42K+ in vitro. By tracer exchange analysis fluxes in both directions were estimated to 8-9 10(-12) mol/cm2. Glucagon in concentrations above 2 x 10(-8) M increased both influx and efflux to 160% of control values. Insulin increased influx by 12-14%, whereas efflux was apparently unaffected. Using an extracellular marker 51Cr EDTA, intracellular level of some ions was estimated in isolated liver cells: K+ = 172 mmol/kg water, Na+ = 25 mmol/kg water, Cl = 53 mmol/kg water. Cellular water content: 60%. Incubation with insulin for 1 h increased the intracellular concentration of K+ 1.7 mmol/kg water. The results indicate that glucoagon increased primarily the K+-permeability of the cell membrane, while insulin stimulates active K+ transport into the cell.
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PMID:K+ transport in isolated rat liver cells stimulated by glucagon and insulin in vitro. 94 6

Degradation of [125I]iodoglucagon during RIA of glucagon would result in erroneously high values for immunoreactive glucagon (IRG). Normal rat plasma was found to have high activity for glucagon degradation that was not suppressed by the aprotinin and EDTA routinely added to the RIA system. About 30% of the added radioactive glucagon was degraded during RIA in assay mixture at pH 7.4 containing 0.2 ml normal rat plasma, and the IRG value was calculated to be 150-180 pg/ml plasma. The degradation was completely inhibited by addition of 2 mM p-chloromercuriphenyl sulfonate (PCMS) plus 0.25 mM leupeptin as protease inhibitors, and in their presence the IRG value was about 80 pg/ml. The glucagon-degrading activity was about half as much in assay mixture at pH 8.8 as in that at pH 7.4, but the degradation still affected the accuracy of IRG values. When rat plasma was incubated with [125I]iodoglucagon in the assay conditions used for RIA and then subjected to Bio-Gel P-6 filtration, three new peaks of radioactivity were found in low mol wt fractions, with decrease in the peak corresponding to [125I]iodoglucagon, whereas on similar treatment in the presence of PCMS and leupeptin all the radioactivity was recovered in the glucagon fraction. The average recoveries of authentic glucagon as IRG in the absence and presence of the inhibitors were less than 60% and more than 90%, respectively. These findings indicate that determination of plasma IRG in rats by RIA with assay mixture containing aprotinin gives spuriously high values owing to degradation of the radiotracer, and that PCMS and leupeptin should be added to the sample and assay mixture to prevent this degradation.
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PMID:Degradation of [125I]iodoglucagon by normal rat plasma in radioimmunoassay mixture containing aprotinin and its prevention by p-chloromercuriphenyl sulfonate and leupeptin. 242 96

To evaluate the effect of glucagon degrading activity (GDA) on radioimmunoassay (RIA) of glucagon, I measured GDAs in plasma, serum, lysed red blood cells (RBC), and suspension of mononuclear cells and granulocytes. Serum levels of GDA in patients with various diseases were also examined. 1. Serum GDA values in normal subjects (control) measured by TCA precipitation method were 4.6 +/- 2.2% (mean +/- S.D.). GDA values in plasma treated with citrate and those in serum treated with aprotinin were not different from those in nontreated serum. GDAs in plasma treated either with EDTA and aprotinin or with EDTA alone were significantly lower than those in control serum, but the values in plasma treated with heparin were markedly higher than those in control serum. 2. GDAs in RBC lysate and suspension of mononuclear cells and granulocytes remained low up to the concentration of 23 X 10(4) RBC/microliters and 5000 mononuclear cells or granulocytes/microliters, respectively. GDAs in RBC lysate and mononuclear cells were markedly suppressed by the treatment with EDTA, whereas GDAs in granulocytes were inhibited by the treatment with aprotinin. 3. Markedly high values of GDA were obtained in serum of patients with pancreas diseases, liver diseases, renal diseases and hyperthyroidism. However, in four patients these elevated levels were restored to normal value after recovery from these disorders. The elevated GDA values in serum were suppressed to normal value by the addition of EDTA and aprotinin. 4. On Bio-Gel P-6 column chromatography, 125I-glucagon incubated with patient serum containing high GDA values revealed several peaks eluted after 125I-glucagon. 5. In healthy subjects, immunoreactive glucagon (IRG) levels in nontreated serum were not different from those in plasma treated either with EDTA and aprotinin or with heparin. 6. In patients showing high serum GDA levels, serum GDA levels were not significantly related to IRG levels in plasma treated with EDTA and aprotinin. These results indicate that a series of treatment of blood samples before assay: addition of EDTA and aprotinin to the blood samples, immediate separation of plasma from blood cells, and storage at 4 degrees C is recommended to avoid breakdown of glucagon by GDAs.
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PMID:[Glucagon degrading activity]. 247 36

To extend the knowledge about systemic glucagon metabolism, intact human erythrocytes were tested for association and degradation of glucagon. When erythrocytes were incubated at 37 degrees C in 0.15 M NaCl solution, glucagon and 125I-glucagon were degraded, depending both on time and hematocrit. At a hematocrit of 0.45, about 20% of 1 nM initial glucagon were degraded during 4 h of incubation. Furthermore, cellular association of glucagon took place amounting to about 10% of the initial glucagon. Nearly 3% of the initial glucagon, but 40% of the cell-associated hormone were found to consist of intracellularly accumulated glucagon degradation products. Despite of nondetectable hemolysis after 60 min of incubation at 37 degrees C, a glucagon-degrading activity was eluted from the cells into the medium. This degrading activity was quantitatively inhibited by Contrykal, EDTA, and o-phenanthroline. Both glucagon degradation and association by human red cells were quantitatively inhibited by bacitracin. These results provided evidence for a participation of human erythrocytes in glucagon metabolism in vitro.
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PMID:[Degradation and association of glucagon by intact human erythrocytes]. 261 24


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