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 direct time-resolved fluorescence anisotropy of the single tryptophan residue in the polypeptide hormone adrenocorticotropin-(1-24) (ACTH) and the fluorescence decay kinetics of this residue (Trp-9) are reported. Two rotational correlation times are observed. One, occurring on the subnanosecond time scale, reflects the rotation of the indole ring, and the other, which extends into the nanosecond range, is dominated by the complex motions of the polypeptide chain. The fluorescence lifetimes of the single tryptophan in glucagon (Trp-25) and the 23-26 glucagon peptide were also measured. In all cases the fluorescence kinetics were satisfied by a double-exponential decay law. The fluorescence lifetimes of several tryptophan and indole derivatives and two tryptophan dipeptides were examined in order to interpret the kinetics. In close agreement with the findings of Szabo and Rayner [Szabo, A. G., & Rayner, D. M. (1980) J. Am. Chem. Soc. 102, 554-563], the tryptophan zwitterion exhibits emission wavelength dependent double-exponential decay kinetics. At 320 nm tau 1 = 3.2 ns and tau 2 = 0.8 ns, with alpha 1 = 0.7 and alpha 2 = 0.3. Above 380 nm only the 3.2-ns component is observed. By contrast the neutral derivative N-acetyltryptophanamide has a single exponential decay of 3.0 ns. The multiexponential decay kinetics of the polypeptides are discussed in terms of flexibility of the polypeptide chain and neighboring side-chain interactions.
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PMID:Time-resolved fluorescence and anisotropy decay of the tryptophan in adrenocorticotropin-(1-24). 626 89

The metabolic effects of a protein-rich meal were studied for 3 h in 10 controls and in 20 cirrhotic patients. After protein ingestion, blood glucose did not vary significantly. Insulin and glucagon levels rose in controls and, more markedly, in cirrhotics. Aromatic amino acids and tryptophan increased more in cirrhotics as a result of their decreased liver function. Similarly, branched-chain amino acids increased by 153 +/- 14 nmol/ml X min (mean +/- SE) in controls and by 259 +/- 27 nmol/ml X min in cirrhotics (p less than 0.02), in the presence of a markedly increased insulin response. Branched-chain amino acid metabolism mainly occurs in skeletal muscle under insulin control; in cirrhosis, it might be reduced as a consequence of insulin resistance. To support this hypothesis, the effects of the protein meal were compared with those of an oral glucose load in 15 cirrhotic patients. Branched-chain amino acid response to protein ingestion significantly correlated with blood glucose response to oral glucose (r = 0.714), and with insulin resistance during the glucose tolerance test, when assessed by the insulinogenic index (r = 0.628). Similarly, in 8 patients, increased branched-chain amino acid response also correlated with the index of tissue sensitivity to insulin obtained by means of the glucose clamp technique during continuous insulin infusion (r = -0.809). We conclude that liver cirrhosis is characterized by an abnormal branched-chain amino acid response to protein ingestion, which matches the well-known intolerance to oral glucose. Both alterations are possibly due to decreased peripheral insulin activity on substrates.
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PMID:Plasma amino acid response to protein ingestion in patients with liver cirrhosis. 634 56

L-tryptophan was given to fasted rats intragastrically or intravenously at a dose of 500 of 166 mg/kg b.w., respectively. Mean (+/- SEM) plasma insulin levels rose after both stimuli and at 10, 30 and 45 min were 63 +/- 26, 86 +/- 25, 48 +/- 7 mU/l after oral, and 28 +/- 4, 25 +/- 6, 19 +/- 6 mU/l after intravenous administration, respectively; plasma tryptophan levels at the above intervals during the oral study were 27%, 60% and 128%, respectively of those during the intravenous study. Plasma GIP levels rose only after intragastric tryptophan administration, and plasma GLI levels did not change in response to either intragastric or intravenous tryptophan. Intragastric tryptophan consistently raised plasma pancreatic glucagon levels which were significantly higher than those observed in control rats given saline, 5, 10, 30 and 45 min after administration. The rise in plasma glucagon was attributed to the glucagonotropic effect of GIP.
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PMID:The differential effect of intragastric and intravenous tryptophan on plasma glucose, insulin, glucagon, GLI and GIP in the fasted rat. 637 8

Investigations were made on the effects of catecholamine (Cat) infusions with and without ammonia (NH3) on plasma and brain amino acids (AA) and brain neurotransmitters in dogs. Groups of four dogs were infused for 5 h with epinephrine (E), epinephrine + norepinephrine (E + NE), epinephrine + norepinephrine with NH3 during h 4 and 5 (E + NE + NH3), epinephrine + norepinephrine + tryptophan with NH3 during h 4 and 5 (T + E + NE + NH3), or saline (C). Cat decreased (P less than 0.05) plasma Gly, Thr, Lys, Pro, Val, Ser, Arg, Leu, Trp, Phe, Asn, Tyr, Met, Ile, Cit, and Asp. The decreases at h 3 for all were to a mean of 45% of 0 h and were associated with no changes in plasma insulin or glucagon. Cat increased plasma Tau and Orn. Of the most abundant brain AA (82% of total), E + NE + NH3 had no effect (GABA, Asp, Gly, Ala, p-ethanolamine) or increased (Glu, Gln, Tau) brain levels. These AA were unchanged by Cat alone. Of the remaining brain AA, most were decreased by Cat (7 of 16, P less than 0.05) and E + NE + NH3 increased brain Trp but had no effect on brain serotonin, 5-hydroxyindoleacetic acid, or NE. Cat changed plasma AA in a way similar to changes produced by NH3 infusion and seen with hepatic insufficiency due to portacaval shunts and nitrosamine-induced pathology. Cat reduced brain AA levels, and this was partially restored by NH3.
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PMID:Effects of catecholamines and ammonia on plasma and brain amino acids in dogs. 646 11

Significant amounts of immunoreactive glucagon (IRG) were determined in acid-ethanol and acid-saline extracts of human thyroid. Glucagon content of healthy thyroid, expressed as ng/g wet tissue or pg/mg protein, was significantly greater after an acid-alcohol extraction than after an acid-saline one. Furthermore IRG in acid-alcohol extracts of healthy tissue was greater than in acid alcohol extracts of diseased thyroid, while with an acid-saline procedure glucagon content was greater in the extracts of pathological tissues. No significant differences in the IRG content between calcified or follicular thyroid nodules and nodular goiter were found. Aliquots of the tissue extracts, fractionated on Bio-Gel P-30 or Sephadex G-100 columns, gave a 3,500 mol wt immunoreactive peak suggesting the existence of a polypeptide with the same size and immunological properties as pancreatic glucagon. Also, active glucagon synthesis by pieces of thyroid was established by the incorporation of L3-H-tryptophan into a 3,500 mol wt polypeptide with specific immune reaction to 30K antiserum. These results suggest that thyroid gland could represent a source of extrapancreatic glucagon in men, and therefore contribute to the circulating levels of this hormone.
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PMID:Presence of immunoreactive glucagon in healthy and diseased human thyroid. Evidence of glucagon synthesis by this gland. 648 80

In an attempt to determine the ability of rat submaxillary glands to synthesise glucagon via protein intermediates, isolated cells from these glands were incubated in vitro with 3H-L-tryptophan and the acid-ethanol extracts of the cells were purified on Bio-Gel P-30 columns. Aliquots of the eluates were incubated with a C-terminal glucagon antiserum (30K) and the radioactivity bound to the glucagon antibody appeared to be distributed among proteins of Molecular weight greater than 40.14 and 3.5 Kdaltons. A similar elution pattern was obtained in the presence of urea (7 mol/l) and guanidine hydrochloride (6 mol/l). To determine the molecular weight of the immunoreactive material eluting before the 3.5 Kdalton polypeptide, aliquots of the cell extracts were immunoprecipitated and analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Polypeptides of 125.8, 63.1, 42.6 and 14.4 Kdaltons were obtained. These polypeptides incorporate more radioactive tryptophan with increase in the time of incubation. Pulse-chase experiments with unlabelled tryptophan, cycloheximide-treatment of isolated cells and limited tryptic digestion of the larger glucagon immunoreactive component, transform it into a 3.5 Kdalton polypeptide with immunological characteristics indistinguishable from pancreatic glucagon. These results suggest that the larger molecule contains glucagon and thus may serve as a precursor or an intermediate of extrapancreatic glucagon biosynthesis.
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PMID:Evidence of glucagon biosynthesis involving protein intermediates in rat salivary glands. 651 May 94

Tryptophan uptake, hydroxylation, and decarboxylation in isolated synaptosomes were studied to assess how their properties may determine the rate of serotonin synthesis in the presynaptic nerve terminals of the brain. Simultaneous measurements of the rates of uptake, hydroxylation, and decarboxylation in the presence and absence of various inhibitors showed that tryptophan hydroxylase is rate-limiting for serotonin synthesis in this model system. There was significant direct decarboxylation of tryptophan to tryptamine. Measurement of tryptophan hydroxylase flux with varying internal concentrations of tryptophan allowed the determination of the Km of tryptophan hydroxylase in synaptosomes for tryptophan of 120 +/- 15 microM. Depolarisation of synaptosomes with veratridine caused both a reduction in the internal tryptophan concentration and an apparent activation of tryptophan hydroxylase. This activation did not occur in the absence of Ca2+ or in the presence of trifluoperazine. Synaptosomal serotonin synthesis and brain stem-soluble tryptophan hydroxylase were inhibited by low concentrations of noradrenaline or dopamine. Dibutyryl cyclic AMP, glucagon, insulin, and vasopressin were observed to have no effect on tryptophan uptake or hydroxylation in synaptosomes.
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PMID:Tryptophan uptake and hydroxylation in rat forebrain synaptosomes. 669 97

The interaction of glucagon and phenylalanine mediated by the OH . radical causes formation of higher molecular weight products of glucagon and phenylalanine, loss of amino acid residues in glucagon, and formation of adducts of glucagon and phenylalanine. The relative yields of these products depend upon the molar ratio of phenylalanine to glucagon in solution. At low ratios, glucagon aggregation and loss of amino acid residues predominate; at high ratios, the formation of phenylalanine dimers (and possible trimers and tetramers) predominates. The formation of adducts reaches a maximum at a phenylalanine:glucagon molar ratio of 3-4, and then decreases gradually, as the molar ratio increases, but is still discernible even at high molar ratios. Mechanisms for the formation of adducts are suggested. The influence of the primary aqueous radical intermediates, OH., H., and e-aq, on adduct formation has been evaluated for several different amino acids by irradiating in the presence of specific radical scavengers. For the aromatic amino acids (phenylalanine, tryptophan, and tyrosine), OH. is considerably more effective than e-aq for mediating adduct formation, whereas for histidine and methionine, these primary radicals are equally effective.
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PMID:Gamma-radiation-induced interactions between amino acids and glucagon. 669 44

To show that glucagon, glucagonlike immunoreactivity (GLI), and insulin are synthetized by organs other than the pancreas and the gastrointestinal tract, different rat tissue acid-ethanol extracts were obtained and analyzed by immunoassay using specific antisera. Significant amounts of glucagon were found in the gastrointestinal tract (44.77 +/- 5.4 ng), salivary glands (1.50 +/- 0.17 ng), thymus (2.80 +/- 0.46 ng), thyroid (0.25 +/- 0.02 ng), and adrenal glands (0.25 +/- 0.06 ng). Whereas GLI appeared in the gut mucosa, adrenal and salivary glands, genuine insulin was detected only in the pancreas. Aliquots of the tissue extracts, fractionated on Bio Gel P 30 columns, gave a 3,500 mol wt immunoreactive (30 K) peak that behaved as pancreatic glucagon on acrylamide gel electrophoresis and displaced 125I-labeled glucagon previously bound to its hepatic receptors. Arginine, epinephrine, and low glucose concentrations stimulated glucagon release from parotid, thymus, and thyroid. Active glucagon biosynthesis by these organs was established by the incorporation of L-[3H]tryptophan into a 3,500 mol wt polypeptide with specific immune reaction with 30 K antiserum. These results suggest that different rat tissues can contribute to the circulating levels of glucagon and GLI and therefore to metabolic homeostasis.
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PMID:Tissue distribution of glucagon, glucagonlike immunoreactivity, and insulin in the rat. 698 65

Monolayer cell cultures from pancreatic islets of aging 129/J strain diabetes (db3J/db3J) and lean littermate control mice were tested for differences in glucagon and insulin secretion in either serum-free Eagle's minimal essential medium (MEM) or Dulbecco's modified minimal essential medium (DMEM). There was a highly significant (p less than 0.0001) main effect of genotype and type of culture medium on glucagon secretion with time. Thus, although numbers of A-cells were not demonstrably increased in db3J/db3J cultures in DMEM, mean medium glucagon levels increased 2.7-, 18-, and 32-fold above littermate normal culture levels at days 4, 6, and 8 respectively. In MEM, the two populations could not be discriminated on the basis of glucagon secretion. By contrast, insulin secretion over culture days showed a highly significant (p less than 0.0001) dependence on genotype, but not type of medium, with the B-cell enriched db3J/db3J preparations secreting between 20 and 30 times as much insulin as controls in both medida. Analysis revealed that the heightened secretory responsiveness of mutatn A-cells in DMEM as compared to MEM was primarily elicited by the elevated DMEM amino acid concentration and specifically lysine (0.8 mmol/l in DMEM versus 0.4 mmol/l in MEM). In pulse-chase experiments using 14 day db3J/db3J cultures, incorporation of 3H-tryptophan into protein that eluted from Biogel P-10 columns in the native glucagon peak indicates that DMEM stimulated glucagon biosynthesis as well as secretion. This study reveals an augmented sensitivity of db3J/db3J A-cells to stimulation by basic amino acids in long-term culture.
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PMID:A new mutation (db3J) at the diabetes locus in strain 129/J mice. II. Studies of pancreatic alpha cell function in culture. 699 70


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