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

In the rat hepatocyte, whether freshly separated or in primary culture, we do not find L-glutamine entry by Systems A and ASC as seen in cells previously studied. Instead the mediated entry of glutamine appears to occur exclusively by a Na+-dependent system ("N") apparently specific to amino acid amides and L-histidine; however, a portion of asparagine uptake occurs by System A. The simplest evidence for the separateness of the added system is the failure of model substrates for System A (e.g. N-methylalanine) to inhibit glutamine uptake significantly, and the failure of glutamine to inhibit the uptake of L-cysteine, model substrate for System ASC, at least in this cell. As is the case for cysteine, glutamine inhibits transport by System A (although not competitively), even though showing no transport by that system. Our finding confirms an earlier inference that glutamine uptake by this cell may follow a route not taken by alanine or serine, and explains the apparently erroneous companion inference that glutamine also shares a route with these two amino acids. Its uptake has now been characterized to show a series of differences from Systems A and ASC. Especially significant in view of the importance of glutamine metabolism are an insensitivity of the new system to stimulation by either insulin or glucagon, and its distinct enhancement (not as large as that for System A) on starvation of the cells with respect to amino acids. Hence, a second system has been found to show adaptive regulation.
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PMID:Characteristics of an amino acid transport system in rat liver for glutamine, asparagine, histidine, and closely related analogs. 737 63

The synthesis of the heterobifunctional cross-linking reagent 2-nitro-4-azidophenylsulfenyl chloride (NAPSCl) is described. This reagent can be used to specifically attach a photoactivatable nitrophenyl azide to tryptophan-containing polypeptides and proteins lacking sulfhydryl groups. The sulfenyl chloride group of NAPSCl reacts with the indole ring of tryptophan following second-order reaction kinetics in 50-100% acetic acid. The labeled product can be effectively photolyzed at wavelengths above 300 nm. The reaction of glucagon, a peptide hormone containing a single tryptophan residue at position 25 and no cysteine, with NAPSCl gave one major product, the photosensitive derivative glucagon-NAPS. The structure and properties of the purified derivative were established by amino acid analysis, absorption spectroscopy, and photolysis. Only the tryptophan residue of this derivative was modified. The photosensitive glucagon was shown to activate the adenylate cyclase of hepatocyte plasma membranes to the same extent as the native hormone at equimolar concentrations. Glucagon-NAPS could be radiolabeled by the lactoperoxidase-catalyzed iodination of the peptide. A glucagon-specific antibody bound both radiolabeled glucagon and glucagon-NAPS peptides. The covalent labeling of protein molecules with radiolabeled glucagon-NAPS peptide upon photolysis was demonstrated. Glucagon-NAPS can be used as an effective photoaffinity probe for labeling the glucagon receptor site in plasma membranes of target cells.
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PMID:Synthesis and characterization of a heterobifunctional photoaffinity reagent for modification of tryptophan residues and its application to the preparation of a photoreactive glucagon derivative. 742 13

A cysteine specific cleavage reaction was used for the preparation of biologically active peptides from recombinant fusion proteins. The fusion protein through cysteine was prepared by a recombinant DNA technology and then treated with cyanylating reagents such as 2-nitro-5-thiocyanatobenzoic acid (NTCB) and 1-cyano-4-(dimethylamino) pyridinium tetrafluoroborate (DMAP-CN) to release the desired product. As an example, we have selected a glucagon-like peptide 1 (7-37) (termed insulinotropin). We constructed an expression vector for a fusion protein in which insulinotropin and human basic fibroblast growth factor (hbFGF) mutein (abbreviated as CS 23) are connected by cysteine and then expressed it in Escherichia coli cells. The fusion protein, after refolding, was purified by heparin affinity chromatography, since CS23 has a strong affinity for heparin. The affinity-purified fusion protein was treated with NTCB or DMAP-CN to give crude insulinotropin, which was then purified by reversed phase (rp) high-performance liquid chromatography (HPLC). From various criteria such as amino acid analysis, amino acid sequence and the biological activity, the purified material obtained was found to be methionylated insulinotropin (Met-insulinotropin) with full activity. The specificity and simplicity of the present method make it versatile and convenient for the preparation of biologically active peptides.
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PMID:A novel procedure for the preparation of biologically active recombinant peptides using a cyanylation reaction. 776 19

Hepatic glutathione concentration is decreased in protein-energy malnutrition. Malnourished rats are able to replenish hepatic glutathione after oral supplementation with L-2-oxothiazolidine-4-carboxylate, a cysteine pro-drug, to levels that are higher than in control rats. These results suggest that, even if a normal amount of amino acids for glutathione synthesis is provided, homeostatic control of glutathione concentration after protein-energy malnutrition is abnormal. The rate limiting enzyme for glutathione synthesis, gamma-glutamylcysteine synthetase, is subject to both short and long term hormonal control. Therefore, we used hepatocytes isolated from weanling rats fed a very low protein diet (0.5 g protein/100 g diet) or a diet adequate in protein for 2 wk to investigate whether a loss of hormonal control could contribute to abnormal regulation of hepatic glutathione. Glutathione concentration in hepatocytes isolated from protein-energy malnourished rats was 82% lower than in controls. In vitro supplementation of isolated hepatocytes with oxothiazolidine-4-carboxylate or methionine increased glutathione concentration in hepatocytes from malnourished rats to concentrations equivalent to control cells. However, when hepatocytes were incubated with cysteine, total glutathione in malnourished rats exceeded that of controls. Treatment of cells from control rats with 50 nmol/L glucagon or 1 mmol/L db-cAMP decreased glutathione concentration by 25-43%. In contrast, the glutathione concentration in hepatocytes of rats fed the low protein diet did not respond to treatment with glucagon or db-cAMP. These data indicate that glutathione synthesis is insensitive to regulation by cAMP in rats with protein-energy malnutrition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of hepatocyte glutathione by amino acid precursors and cAMP in protein-energy malnourished rats. 812 Jun 50

Glutamine transport was studied in preconfluent monolayered, mononucleated myoblasts (4 days old) and in fused, multinucleated, differentiated myotubes (10 days old), both prepared from neonatal rat skeletal muscle. The initial (60 s) rate of 50 microM glutamine uptake in myoblasts and myotubes was stereospecific, saturable, and largely (80%) Na+ dependent. At glutamine concentrations of 0.01-1 mM, Na(+)-dependent uptake showed saturation kinetics: in myoblasts, the Michaelis constant (Km) was 197 +/- 38 microM, maximum velocity (Vmax) was 1,165 +/- 60 pmol.min-1.mg protein-1; in myotubes, Km was 174 +/- 51 microM and Vmax was 1,435 +/- 47 pmol.min-1.mg protein-1. The Na(+)-dependent glutamine uptake was Li+ tolerant in both myoblasts and myotubes. The Na(+)-dependent uptake of 50 microM L-[3H]glutamine was investigated in the presence of various amino acids at 0.01-10 mM. Histidine and asparagine competitively inhibited glutamine uptake, but inhibition by serine was noncompetitive; glutamate, arginine, leucine, and 2-aminobicyclo(2,2,1)heptane-2-carboxylate (BCH) had no significant inhibitory effects; 2-(methyl-amino)isobutyrate (MeAIB) caused a small but significant inhibition. In parallel with a stimulation of glucose transport, addition of insulin stimulated Na(+)-dependent glutamine uptake within 1 h by a maximum of 27% in myoblasts and 42% in myotubes (half-maximal stimulation at 0.3 nM insulin). Glucagon had no effect. Kinetic analysis revealed that the insulin-stimulated increase in glutamine transport was due to a Vmax effect, which was cycloheximide inhibitable. The insulin-stimulated increase was Li+ tolerant and not inhibited by MeAIB or cysteine at 1 mM. The results indicate that the predominant glutamine transporter of neonatal rat skeletal muscle cells in primary tissue culture in System Nm. System Nm also appears to be the major insulin-sensitive glutamine transport component in skeletal muscle. Primary muscle culture appears to be a useful preparation for studying glutamine transport and its regulation.
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PMID:Characteristics of glutamine transport in primary tissue culture of rat skeletal muscle. 833 46

The activities of cathepsin B, L, J and H in rat liver were significantly increased by starvation if compared with normal diet rats. Furthermore, the activity of cathepsin L increased with glucagon treatment, and the activities of cathepsin L and H decreased significantly with insulin treatment. The changes in cathepsin B and J activities showed the same tendencies as those of cathepsin L and H, but the differences were not statistically significant. The changes in the activities of cathepsin B and L on starvation corresponded with the changes of enzyme protein amounts judged from Western blotting analysis. The levels of the lysosomal cysteine proteinases and amino acid deaminases in the liver changed in parallel with the hormonal and dietary conditions. The increases of alanine amino transferase activity (AAT) started from a much earlier stage than those of cathepsins under the starvation condition. Although administration of prednisolone caused marked induction of the deamination enzymes such as AAT, the levels of cathepsins in the liver were not changed.
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PMID:Hormonal and dietary regulation of lysosomal cysteine proteinases in liver under gluconeogenesis conditions. 892 90

A tripeptidyl aminopeptidase I with an M(r) of 47,000 Da has been purified from rat spleen. The N-terminal sequence of the enzyme and internal sequences did not resemble that of any known protein. The enzyme cleaves tripeptides from synthetic substrates provided that the N-terminus is unsubstituted and the amino acid in the P1 position is not charged. The enzyme also cleaves small peptides (angiotensin II and glucagon) releasing tripeptides but does not appear to demonstrate any preference for amino acids on either side of the cleavage site. The enzyme had maximum activity at pH 4 but was unstable above pH 7. Rat spleen tripeptidyl peptidase I was not inhibited by classical inhibitors of serine, cysteine, aspartate or metalloproteinases. The peptidase was potently inhibited by a series of substrate-based tripeptidyl chloromethyl ketones (Ki's of 10(-6)-10(-8) M). Inhibition was rapid and reversible. This mode of inhibition is different to the interaction between chloromethyl ketones and cysteine or serine peptidases. These tripeptidyl chloromethyl ketones were also inhibitors of bone resorption using an in vitro assay suggesting that a tripeptidyl peptidase is involved in the degradation of bone matrix proteins.
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PMID:Purification and characterisation of a tripeptidyl aminopeptidase I from rat spleen. 965 84

Stanniocalcin (STC) is a hormone that was originally identified in fish, where it inhibits calcium uptake by the gills and gut and stimulates phosphate adsorption by the kidney. Recently, two mammalian homologues of stanniocalcin were identified. The first (STC1) shows 61% identity to the fish stanniocalcins and appears to have a function similar to that of the fish stanniocalcins. The second homologue (STC2) is 30-38% identical to the fish stanniocalcins, and is characterized by unique cysteine and histidine motifs that are not found in the other stanniocalcins. We purified both the native hamster and recombinant human STC2 proteins and obtained a partial amino acid sequence of the hamster protein. Both proteins behave as a disulfide bonded homodimer, which undergoes post-translational modification(s). The STC2 gene was localized to human chromosome 5q35. Northern blot analysis revealed that the primary site of human STC2 production is the pancreas, and immunostaining localized the STC2 protein to a subpopulation of cells in the islet. Double immunostaining for STC2 and either insulin or glucagon revealed that STC2 protein is found in the alpha cells, but not the beta cells. We speculate that STC2 may play a role in glucose homeostasis.
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PMID:Stanniocalcin 2: characterization of the protein and its localization to human pancreatic alpha cells. 1045 Aug 31

The effects of glucagon on amino acid transport in rat hepatocytes are not fully understood. We examined the effect of this hormone on alanine, serine and cysteine preferring system (system ASC)-mediated amino acid transport in rat hepatocyte monolayers using 2-aminoisobutyric acid (AIB) and l -cysteine. Glucagon induced a time and protein synthesis-dependent stimulation of Na(+)-dependent alanine preferring system (system A)-independent AIB transport. The glucagon-induced increase in transport activity was not modified by substrate starvation and not related to changes in the intracellular pool of amino acids. Glucagon did not modify system ASC activity measured by l -cysteine. Therefore the transport activity of AIB independent of system A stimulated by glucagon cannot be attributed to system ASC. This suggests a Na(+)-dependent transport system in rat hepatocytes not identified until now.
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PMID:A Na(+)-dependent system A and ASC-independent amino acid transport system stimulated by glucagon in rat hepatocytes. 1052 43


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