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 response of the plasma substrate and hormone profile of survivor and nonsurvivor septic trauma patients to varying rates of amino acid infusion (IVAA) were contrasted. When IVAA=0 levels of most plasma amino acids (except aspartate, tryptophan, cysteine, and proline) were lower in nonsurvivors. At IVAA=1 to 100, however, 11 of 20 plasma amino acids were significantly (p less than or equal to 0.05) higher in nonsurvivors: only glutamate was significantly lower (p less than or equal to 0.001) and valine, isoleucine, and arginine on average lower. At IVAA less than or equal to 101 to 200, only alanine, methionine, tyrosine, and phenylalanine were significantly (p less than or equal to 0.005) higher in nonsurvivors; isoleucine was significantly (p less than or equal to 0.02) lower. The sharp increase in methionine and decrease in tryptophan in nonsurvivors with IVAA was particularly marked. Polynomial regression analysis showed that urea increased significantly with IVAA in both patient groups, while free fatty acids and cortisol decreased only in nonsurvivors. Insulin increased with IVAA only in survivors, glucagon only in nonsurvivors. Triglycerides, glycerol, acetoacetate, beta OH butyrate, and glucose appeared to show no significant response to IVAA in either patient group. The data are consistent with increased peripheral protein catabolism and branched-chain amino acid oxidation in association with decreased tissue uptake of conventional energetic fuels. These results may be interpreted to be consistent with an impairment of mitochondrial translocase systems.
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PMID:Multiple systems organ failure: III Contrasts in plasma amino acid profiles in septic trauma patients who subsequently survive and do not survive-effects of intravenous amino acids. 721 92

Diurnal variation in hepatic levels of lactate, pyruvate, phosphoenolpyruvate (PEP), alpha-ketoglutarate, malate, oxaloacetate, ketone bodies, alanine, serine, glycine, aspartate, glutamate, glutamine, valine, urea, adenine nucleotides and inorganic phosphate were studied in rats adapted to a high protein, carbohydrate-free diet for 24 days. Most circadian rhythms differed in relation to controls (10% protein diet); many merely had different amplitudes, some were inverted, and some exhibited drastically altered patterns. Cytoplasmic redox state exhibited nearly similar variations and phosphorylation state differed primarily in amplitude whereas mitochondrial redox state was highly depressed in the absorptive phase. The metabolic regulation implied by the results is discussed in relation to both circadian variations of plasma insulin and glucagon concentrations, and pyruvate kinase and phosphoenolpyruvate carboxykinase activities previously reported.
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PMID:Circadian variation of liver metabolites and amino acids in rats adapted to a high protein, carbohydrate-free diet. 728 96

Peptidyl chloromethyl ketones, largely derived from arginine, inactivate cathepsin B (beef spleen) at rates that vary 300 fold according to sequence, but the residue in the P1 position is not responsible for this variation since homoarginine or nitroarginine in this position provide inhibitors as good or better than those containing arginine. Peptidyl chloromethyl ketones containing hydrophobic residues such as phenylalanine or valine in the P2 and P3 position are the most effective inhibitors of the group. Cystamine (bis-aminoethyl disulfide) inactivates cathepsin B by formation of a mixed disulfide. Derivatives of cystamine containing phenylalanine, such as bis-N,N'-Phe-cystamine and bis-N,N'-Ala-Ala-Phe-cystamine are more effective and represent a new class of affinity labels for cathepsin B. Immobilized peptidyl cystamine derivatives can be used for the purification of cathepsin B by covalent affinity chromatography. Cathepsin B from beef spleen has a pronounced carboxydipeptidase action on glucagon as described for the human liver enzyme. This action can be conveniently followed by high pressure liquid chromatography.
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PMID:The specificity of cathepsin B. 734 2

Liver RNA and protein breakdown rates were measured simultaneously in fed and in 24 h-fasted rats during a short-term cyclic perfusion, 1 h after an intraperitoneal injection of glucagon or of saline. RNA was labelled in vivo by an intraperitoneal injection of [6-14C]orotic acid, 60 h before the start of the perfusion. The accumulation of radioactive cytidine and valine in the perfusion medium for 15 min was used to determine RNA breakdown and proteolysis respectively. The portal glucagon/insulin ratio was significantly higher in the fasted glucagon-treated rats than in their fed counterparts. Although glucagon administration significantly increased RNA and protein degradation rates in the fasted and in the fed groups, the effect was greater after 24 h of starvation. The relationship between these biochemical changes and the alterations of the hepatocyte lysosomal system was investigated by determining the fractional cytoplasmic volume of lysosomal structures (autophagic vacuoles and dense bodies) by morphometry in the fasted glucagon-treated rats and in their controls. Hyperlucagonaemia significantly enhanced the relative volume of autophagic vacuoles without affecting that of dense bodies. The results showed that hyperglucagonaemia induced in vivo stimulated both liver RNA and protein breakdown and that this effect was modulated by the nutritional status of the rats.
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PMID:Glucagon administration in vivo stimulates hepatic RNA and protein breakdown in fed and fasted rats. 751 68

We have investigated the mitogenic effect of three mutant forms of human insulin on insulin-producing beta cells of the developing pancreas. We examined transgenic embryonic and adult mice expressing (i) human [AspB10]-proinsulin/insulin ([AspB10]ProIN/IN), produced by replacement of histidine by aspartic acid at position 10 of the B chain and characterized by an increased affinity for the insulin receptor; (ii) human [LeuA3]insulin, produced by the substitution of leucine for valine in position 3 of the A chain, which exhibits decreased receptor binding affinity; and (iii) human [LeuA3, AspB10]insulin "double" mutation. During development, beta cells of AspB10 embryos were twice as abundant and had a 3 times higher rate of proliferation compared with beta cells of littermate controls. The mitogenic effect of [AspB10]ProIN/IN was specific for embryonic beta cells because the rate of proliferation of beta cells of adults and of glucagon (alpha) cells and adrenal chromaffin cells of embryos was similar in AspB10 mice and controls. In contrast to AspB10 embryos, the number of beta cells in the LeuA3 and "double" mutant lines was similar to the number in controls. These findings indicate that the [AspB10]ProIN/IN analog increased the rate of fetal beta-cell proliferation. The mechanism or mechanisms that mediate this mitogenic effect remain to be determined.
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PMID:A transgene coding for a human insulin analog has a mitogenic effect on murine embryonic beta cells. 760 77

Recent data revealed the existence, localization and possible function of specific receptors for glucagon-like peptide 1 (7-36) amide (GLP-1) in rat lung. This receptor has different biochemical features than the GLP-1 receptor in endocrine pancreas. Therefore, we aimed to clone the lung receptor cDNA in order to analyze whether biochemical and functional diversity of the GLP-1 receptors in lung and pancreas is based upon genetic differences. A cDNA library from rat lung in a lambda gt11 vector was screened with a cDNA probe coding for the rat pancreas GLP-1 receptor. Thereby, we found a lung GLP-1 receptor cDNA which shows nearly complete homology to the pancreatic beta-cell receptor cDNA. Only one base exchange occurred at base 1 of a codon at position 977 resulting in a change of valine residue for isoleucine at position 323 of the amino acid sequence within the fifth transmembrane region. Northern blot hybridization identified transcripts at 2.7, 3.4, and 3.6 Kb. Expression of the recombinant lung GLP-1 receptor cDNA in CHO cells displayed a pharmacological profile similar to that seen with cells expressing the beta-cell derived cDNA. Therefore, we conclude that tissue-specificity for GLP-1 receptors is based upon posttranslational modifications of the receptor protein (for example glycosilation) or alternative splicing of primary transcripts and not on variations within the coding sequence of the receptor gene.
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PMID:Molecular cloning of a cDNA encoding for the GLP-1 receptor expressed in rat lung. 781 6

The effect of the antilipolytic agent 3,5-dimethylpyrazole (DMP) on liver autophagy and protein degradation was studied on male young adult rats (200 g body wt) of the Sprague-Dawley strain by electron microscopy and short-term single-pass liver perfusion and HPLC amino acid assay in the perfusate. Treatment with DMP (12 mg/kg body wt) enlarged the lysosomal-autophagic compartment in liver cells in 30 min and increased significantly the concentrations of valine and total amino acid in blood plasma (taken at sacrifice) and valine concentration in the liver perfusate in 60 min. These effects of DMP stimulating liver were secondary to the metabolic and endocrine effects of the drug (which caused a decrease in FFA, glucose, and insulin and an increase in glucagon and corticosterone plasma levels with a shorter latency, about 15 min). The effects of DMP were compared to those of other treatments inducing liver autophagy and protein degradation in vivo. Alterations after DMP or glucagon injections were similar, but they were larger and lasted for a longer time with DMP administration. Treatment with vinblastine or chloroquine enlarged the lysosomal-autophagic compartment without increasing protein breakdown.
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PMID:A new method for the investigation of endocrine-regulated autophagy and protein degradation in rat liver. 826 62

Levels of plasma amino acids, ammonia, glucagon and insulin and their 5-hr responses to a protein feeding were evaluated before and sequentially (3 mo and 1 yr) after distal splenorenal shunt in 10 patients with cirrhosis belonging to Child-Pugh's class A or B. An index of glucagon effectiveness (plasma glucose/glucagon) was also calculated. These parameters were related to liver test results, portal vein diameter and mental state, and they were compared with those found in seven patients undergoing sclerotherapy of esophageal varices with comparable liver function (control group). Liver test results and levels of plasma insulin did not change in either group. Shunt significantly increased levels of fasting tyrosine, methionine, ornithine, arginine, histidine, ammonia and glucagon with respect to the control group; it also significantly decreased levels of leucine, valine, glucagon effectiveness and portal vein diameter. The elevation of levels of tyrosine, ammonia and the sum of arginine and ornithine was correlated directly with the increase in glucagon and inversely with the decline in glucagon effectiveness. Tyrosine increase was also correlated with the reduction of portal vein diameter. One shunted patient showed mild hepatic encephalopathy. Protein feeding did not worsen the mental state of patients before and after the operation. Surgery significantly increased the 5-hr response to the meal of gluconeogenic amino acids; its rise was again correlated with the changes in glucagon plasma levels and effectiveness. Although the absorptive levels of plasma ammonia were significantly higher 1 yr after surgery, its 5-hr response barely rose. In cirrhotic patients with a relatively preserved liver function, distal splenorenal shunt progressively worsened the fasting plasma profile of nitrogen compounds and the response to protein ingestion of gluconeogenic amino acids. The decline of portal blood flow and glucagon effectiveness may be causal factors. Despite this, the "cerebral" tolerance to a moderate oral load of protein was not reduced by surgery.
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PMID:Early and late changes in fasting and absorptive plasma amino acids and ammonia after distal splenorenal shunt in cirrhosis. 829 90

Nineteen bulimic women and 22 age-matched controls were randomly assigned to receive 25 g of glucose or a placebo injection under double-blind conditions. Blood samples of glucose, insulin, and glucagon, and psychometric assessments of mood and food cravings were obtained 10 min before, and 0, 5, 10, 20, 30, 45, and 60 min after injection. Blood levels of the large neutral amino acids (LNAAs) tryptophan, tyrosine, leucine, valine, phenylalanine, and leucine were determined at 10 min before and 60 min after the injection. Bulimic subjects were found to report more symptoms of distressed mood throughout the entire monitoring period than controls. Five minutes following glucose ingestion the self-reports of depression, fatigue, anxiety, and bewilderment rose to a level among the bulimic subjects that was above that at baseline, and was higher than that of bulimia nervosa (BN) subjects receiving placebo. No comparable change in mood was observed among controls. Blood glucose levels were correlated with mood in the bulimic group, but not in controls. In addition, the glucose injection induced a heightened urge to binge in the bulimic group (compared to placebo at 10 and 60 min), whereas reducing food cravings (for sweets) in the controls (at 5 min). When collapsed across time and injection condition, the blood glucose level of bulimics was lower than that of controls. There were no differences in insulin response between the groups. The bulimic group was found to have lower baseline levels of blood tryptophan, whereas no differences in the tryptophan/LNAA ratio were observed either at baseline or following glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A double-blind placebo-controlled glucose challenge in bulimia nervosa: psychological effects. 844 64

The effects in vivo of the two major in vitro regulatory aminoacids, leucine and glutamine, on liver protein degradation were explored in male young adult Sprague Dawley rats. Protein degradation was stimulated by the injection of the antilipolytic drug 3,5 dimethylpyrazole (DMP), which rises glucagon and lowers insulin plasma levels. At the appropriate time-points (20 and 40 min) after the injection of DMP, glutamine or leucine (12.5 mg/kg b.w.) were injected intraperitoneally. The rate of liver protein breakdown was evaluated 60 min after the injection of DMP on the basis of the release of valine into the perfusate during a short term single pass liver perfusion. The aminoacid was assayed by an HPLC procedure. Results show that the administration of glutamine inhibited the DMP-induced increase in the rate of valine release from the perfused liver whereas the administration of leucine did not; neither of the aminoacids appeared to have any effect on the metabolic or endocrine changes that are required for the induction of liver autophagy and protein breakdown by DMP. It is concluded that the aminoacid glutamine has a powerful action on the in vivo regulation of liver protein breakdown, which is not apparent with leucine.
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PMID:The regulation of liver protein degradation by aminoacids in vivo. Effects of glutamine and leucine. 854 91


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