Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The action of Armillaria mellea protease has been evaluated on a number of polypeptide substrates. It has been shown to split the Pro7-Lys8 bonds in both native and oxidised lysine-vasopressin and the Ser11-Lys12 bond in glucagon. No other splits were detected in these substrates. The enzyme also caused extensive degradation of S-carboxymethyl lysozyme, S-carcoxymethyl pepsinogen and oxidised ribonuclease. A. In each case the only new amino-terminal residue to appear was lysine. A. mellea protease was inhibited by the chelating agents 1,10-phenanthroline, alpha, alpha'-bipyridine and imidazole. The pK1 values (negative log10 of concentration required for 50% inhibition) for these three inhibitors were 3.9, 3.4 and 1.1, respectively. Lysine, S-2-aminoethylcysteine and short chain aliphatic amines also proved to be relatively good inhibitors of A. mellea protease while arginine was a poor inhibitor.
 ...
PMID:Specificity and inhibition studies of Armillaria mellea protease. 2 49

Sepsis is a major catabolic insult resulting in modifications in carbohydrate and fat energy metabolism, and leading to increased muscle breakdown and nitrogen loss. Insulin resistance, which develops in sepsis, decreases glucose utilization, but plasma insulin levels are sufficiently elevated to prevent lipolysis, resulting in a further energy deficit. The availability of fuels in sepsis is therefore limited, and the body resorts to muscle breakdown, gluconeogenesis, and amino acid oxidation for energy supply. Previous work has not defined, however, the exact alterations in amino acid metabolism. Therefore, the following studies were undertaken. Blood samples were drawn from fifteen patients in whom the diagnosis of sepsis was clinically established; the samples were analyzed for amino acid, beta-hydroxyphenylethanolamines, glucose, insulin and glucagon concentrations. The plasma amino acid pattern observed was characterized by an increase in total amino acid content, due mainly to high levels of the aromatic amino acids (phenylalanine and tyrosine) and the sulfur-containing amino acids (taurine, cystine and methionine). Alanine, aspartic acid, glutamic acid and proline were also elevated, but to a lesser degree. The branched chain amino acids (valine, leucine and isoleucine) were within normal limits, as were glycine, serine, threonine, lysine, histidine and tryptophan. Those patients who did not survive sepsis had higher levels of aromatic and sulfur-containing amino acids as compared to those patients surviving sepsis. On the other hand, those patients surviving sepsis had higher levels of alanine and the branched chain amino acids. In a second group of five patients with overwhelming sepsis accompanied by a state of metabolic encephalopathy, a parenteral nutrition solution consisting of 23% dextrose, and an amino acid formulation enriched with branched chain amino acids was administered. In these five patients, normalization of the plasma amino acid pattern and reversal of encephalopathy was observed. The following sequence of events may be postulated: The septic patient develops insulin resistance in the peripheral tissues, primarily muscle, while the adipose tissue is much less affected. The insulin resistance and the inability to utilize fat leads to increased muscle proteolysis. Muscle breakdown results in release into the blood of enormous amounts of various amino acids; the muscle itself is able to oxidize the branched chain amino acids, supplying the muscles' own energy requirements and alanine for gluconeogenesis. The extensive muscle proteolysis coupled with relative hepatic insufficiency occurring early in sepsis results in the appearance in the plasma of high levels of most of the amino acids present in muscle, particularly the aromatic and the sulfur-containing amino acids. The outcome of patients with sepsis might be positively affected by combined therapy with glucose, insulin and branched chain amino acids.
 ...
PMID:Amino acid derangements in patients with sepsis: treatment with branched chain amino acid rich infusions. 9 98

Splenic lobes from the pancreas of newborn rats (48-64) hr. were used for the in vitro investigation of cyclic AMP, glucose and amino acid interaction in hormonal secretion. The slight discrepancy found in glucagon relaease with radioimmunoassay and binding assay to specific receptors in liver does not affect the ratio of stimulated to control values. The insulin release due to gheophylline dibutyrl cyclic AMP (dbcAMP) or to arginine is glucose-dependent as in adult rats and provides an index for the validity of the preparations. Glucose alone is efficient in stimulating insulin release but does not affect glucagon secretion; however simultaneous addition of 10 mM arginine, alanine, and lysine (A.A.) or of arginine alone resulted in a higher glucagon release at 1.6 mM than at 16.7 mM GLUCOSE. Theophylline (5 mM)and dbcAMP (2mM) induced a 2=fold increase in glucagon release at low or hight glucose concentrations . Incubation of theophylline (10 mM) and A.A. or arginine resulted in a considerable increase in glucagon release. Potentation of the 3 A.A.-induced glucagon reby dbcAMP was about 1800% no matter what the glucose concentration; similar observations were made for insulin with a 700% potentiation of the 3 A.A.effect glucagon was released more effectively by dbcAMP than was insulin,whereas the reverse was observed with theophylline. These findings suggest that knowledge of the cyclic AMP content is essential when assessing the influence of substrates on glucagon release. The combination of substrates with cyclic AMP clearly demonstrated that potentiation of glucagon release occurs mainly with amino acids, whereas for insulin occurs mainly with amino acids, whereas for insulin release it is mainly glucose which potentiates release.
 ...
PMID:Interaction of amino acids and cyclic AMP on the release of insulin and glucagon by newborn rat pancreas. 16 77

The effect of injection of glycogenolytic enzymes on tissue glycogen, blood glucose and plasma insulin was studied in mice. No effects were observed following phosphorylase, whereas the hydrolytic enzymes, alpha-amylase and acid amyloglucosidase depressed liver glycogen. In addition acid amyloglucosidase induced a decrease in blood glucose, a slight elevation of plasma insulin and a marked increase in tolbutamide-stimulated insulin release. At the doses given none of the enzymes affected muscle glycogen. Amyloglucosidase pretreatment markedly enhanced insulin release induced by glibenclamide, leucine, isoleucine, lysine and glucose whereas insulin release stimulated by IPNA, ACTH, glucagon and "CCK-PZ" was unaffected. Injection of acid amyloglucosidase has a profound influence on carbohydrate content and regulation in mice. It is suggested that the dependence or independence of amyloglucosidase activity among the insulin secretagogues tested might reflect different or partially different mechanisms in the process of insulin secretion.
 ...
PMID:Carbohydrate content and regulation following injection of different glycogenolytic enzymes. 16 77

Several procedures have been reported for the assay of corticotrophine-releasing factor (CRF), each having its advantages and disadvantages. This report deals with an in vitro assay of ACTH releasing activity utilizing pituitary incubation combined with ACTH radioimmunoassay. Rat half pituitary was preincubated in 2 ml Krebs Ringer bicarbonate buffer containing 0.2% glucose and 0.25 % BSA (KRBG-BSA) for 1.5 hr (45 min X 2). The medium was replaced by 1 ml KRBG-BSA and incubated for 30 min. Then the medium was again replaced by 1 ml KRBG-BSA or KRBG-BSA containing test materials and incubated for another 30 min. The amount of ACTH assayed by radioimmunoassay in the 2nd 30 min incubation was compared with in the 1st 30 min incubation and expressed as percentage. In ACTH radioimmunoassay, anti-ACTH serum was diluted to 1 : 1,500-3,000. The 125I-alpha 1-24ACTH-antibody system was not affected by lysine-vasopressin (LVP), arginine-vasopressin (AVP), rat's pituitary LH, GH and prolactin. Human 1-39ACTH was used as ACTH standard, and the dilution curve of incubation medium was paralleled with the standard curve. Repeatability of immunoassayable ACTH within-assay was 174 +/- 5.0 pg/tube (CV = 2.9%). A log dose-relationship was observed between the amounts of stalk median eminence extracts (SME ; NIAMDD) added to the incubation medium and its ACTH releasing activities. The sensitivity of this assay method was at least 0.1 SME or 10 mU of LVP and AVP. Using this method, it found that LVP, AVP, norepinephrine (100 ng/ml200 ng/ml) and 5-hydroxytryptophane (1 mug/ml) had ACTH releasing activities but LH-RH, TRH, glucagon, dopamine, phentolamine, propranolol, haloperidol, prostaglandin E1 and indomethacin did not affect the release of ACTH.
 ...
PMID:[In vitro assay for ACTH-releasing activity using ACTH radioimmunoassay: ACTH releasing activities by various drugs (author's transl)]. 18 1

The glucagon and insulin release induced by amino acids was studied in the presence of glucose, dibutyryl cyclic AMP (dbcAMP) or theophylline on the splenic part of the pancreas of new born rats (48 to 64 hours). The results were compared to the literature data. Arginine or a mixture of the three amino acids (A.A.), arginine, lysine or alanine, stimulate glucagon secretion at 1.6 mM glucose. This stimulation is suppressed by 16.7 mM glucose. On the other hand, 16.7 mM glucose potentiates the effect of arginine or of the 3 A.A. on insulin release. At 1.6 mM glucose, theophylline potentiates the effect of 3 A.A. (10 mM each) on glucagon and insulin release : this effect reaches a maximum at 5 mM of theophylline; dbcAMP also potentiates the effect of 3 A.A. on glucagon and insulin release, and the effect of arginine, alanine or lysine on glucagon release. On the beta cell, the lack of potentiation observed between dbcAMP and arginine, lysine or alanine indicates that these A.A. interact positively when mixed together. In the presence of arginine or of the three A.A., the percentage stimulation of glucagon and insulin release depends on the dbcAMP dose and does not vary with the glucose concentration. The increase of glucagon and insulin release observed when the NaCl concentration in the incubation medium decreases cannot account for our results. Cyclic GMP (4 mM) does not modify the glucagon or insulin secretion induced by different concentrations of glucose or by the mixture of A.A. (10 mM each). The stimulating effect of acetylcholine on insulin release would not be related to the cyclic GMP molecule. In conclusion, instead of modifying the specificity of substrate, theophylline or dbcAMP accentuate it: glucose stimulates specifically the beta cell whereas 3 A.A. are more effective on the alpha2 cell than the beta cell. Cyclic AMP suppresses the glucose effect on glucagon release induced by the amino acids. Because of its interaction with glucose and amino acids, cyclic AMP seems to be a very important element in the regulation of the release of these pancreatic hormones.
 ...
PMID:Regulation by glucose and cyclic nucleotides of the glucagon and insulin release induced by amino acids. 18 41

Radioimmunoassay of cyclic AMP (cAMP) in the islets of Langerhans from 48-64 h old Rats was performed after succinylation of the samples. cAMP was detected at 0.03 nM. The cAMP content of islets increases when L-arginine, L-lysine and L alanine are added together in the incubation medium at a concentration of 5-10 mM each. When phosphodiesterase is inhibited by theophylline the three amino acids considerably increase the cAMP content of islets. Thus an increase in cAMP content of the islets was observed with a concentration of amino acids which is efficient in stimulating the insulin and glucagon secretion.
 ...
PMID:[Measurement of cyclic AMP in the islets of Langerhans of newborn rats. Effect of amino acids]. 19 68

The fasting normal human volunteer subject provides an ideal experimental setting for the initial investigation of foodstuffs whose use is proposed for the acutely ill surgical patient. In the normal human subject many variables can be controlled; the achievement of an ideal body fuel economy is quite simple; if a favorable utilization of injected foodstuffs cannot be achieved in this setting, it is unlikely, and remains to be proven, that utilization will be satisfactory under the challenges of acute surgical trauma. In this experimental model, employing four normal human volunteer subjects, nutrition has been provided by the intravenous infusion of isotonic amino acids (FreAmine(R) II) at a 3.4% concentration. No other source of calories or nutrients was provided. In this setting, utilization was very poor; the subjects were in negative nitrogen balance throughout. The nitrogen excretion was significantly greater than the total of infused nitrogen. The changes in protein, fat and carbohydrate intermediates, as well as the alteration in hormone concentrations, suggest the following endocrine governance of fuel economy in this setting: a sharp rise in glucagon with maintenance of insulin concentration; rapid gluconeogenesis at the expense of both injected and endogenous amino acids; a progressive ketosis without any associated improvement in protein economy; fat oxidation to meet caloric need. The changes in plasma amino acid concentrations are of outstanding interest. They demonstrate changes appropriate to the infusion gradient with the exception of three amino acids whose concentrations did not respond to high infusate levels (serine, lysine, and alanine); likewise, by the fact that methionine rose remarkably though present in only low concentrations in the infusion. These data, taken with other information reported in the literature, as well as continuing studies in these laboratories, strongly suggest that the utilization of infused amino acids for protein synthesis is favored by the provision of an additional caloric source such as glucose.
 ...
PMID:Intravenous amino acids as the sole nutritional substrate. Utilization and metabolism in fasting normal human subjects. 40 64

Specific modification of the single lysine residue (Lys-12) in glucagon with O-methylisourea has been effected by blocking the reactivity of the amino terminal histidine with copper, providing a method for obtaining [12-homoarginine]glucagon. It was found that as a side reaction, under the conditions of the modification reaction, Cu(II) catalyzed cleavage of the polypeptide chain between Asp-9 and Tyr-10, and between Lys-12 and Tyr-13. This observation may be of value for development of a sequence-specific peptide cleavage procedure. The dilute solution conformations of glucagon and [12-homoarginine]-glucagon were compared by circular dichroism, fluorescence, phosphorescence, energy transfer, and optical detection of magnetic resonance. The results indicate that conversion of Lys-12 to homoarginine does not alter the helix content the side chain conformation in the vicinity of the tyrosine and tryptophan residues, or the relative distances and orientations between these residues. However, the modification reduces the hormone potency towards activation of lipolysis in isolated rat epididymal fat cells by a factor of seven. We attribute the loss of potency to an interference with a specific interaction between the lysine residue and the fat cell hormone receptor, and not to a change in the solution conformation of the hormone.
 ...
PMID:[12-Homoarginine]glucagon: synthesis and observations on conformation, biological activity, and copper-mediated peptide cleavage. 42 94

In ten patients with a femoral shaft fracture, arterial plasma amino acids and glucagon, blood glucose, and serum insulin were measured after an overnight fast on the third, fifth, and seventh days following injury. Ten normal subjects were controls. On all days, concentrations of the key glucogenic amino acid, alanine, were the same in both groups, but levels of another glucogenic amino acid, glycine, were significantly less in the fracture patients. Other amino acid changes following injury were maximal at 7 days, with significant elevations of phenylalanine, methionine, tyrosine, ornithine, lysine, arginine, valine, isoleucine, and leucine. Increased levels of insulin, glucose, valine, isoleucine, and leucine on the fifth and seventh days after injury implied insulin resistance. Plasma glucagon was elevated on the third (p less than 0.05) and seventh (p less than 0.01) days after injury, but the concentrations measured are insufficient to explain the impaired carbohydrate tolerance following a fracture.
 ...
PMID:Arterial plasma amino acids during the first week following femoral shaft fracture. 43 79


1 2 3 4 5 6 7 8 9 10 Next >>