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)

This study was performed to assess the relationships between prohormone transport and processing in separate cell types in pancreatic islet tissue. Anglerfish islets were subjected to pulse-chase incubation with [3H]tryptophan and/or [35S]cysteine. Tissue and media were removed at specific time points during the incubation and prepared for electron microscopic examination or biochemical analysis. Specific islet cell types were identified ultrastructurally using protein A gold immunocytochemistry. Transport of newly synthesized peptides through specific subcellular compartments was monitored using electron microscopic autoradiography. Prohormone-product ratios were established by gel filtration and high-performance liquid chromatography analyses of tissue extracts. Complete analyses were performed on A-cells (source of proglucagon-II, glucagon-II, and glucagon-like peptide-II), B-cells (proinsulin and insulin), D-cells (prosomatostatin-II and somatostatin-28), and S-cells (prosomatostatin-I and somatostatin-14). Transport of newly synthesized peptides proceeded from rough endoplasmic reticulum (RER) to Golgi complex and then to mature secretory granules in all cell types. The transport rate was most rapid in A- and B-cells, slower in S-cells, and slowest in D-cells. The T1/2 for conversion of prohormone to product(s) was shortest in S-cells (150 min), slightly longer in B-cells (155 min), much longer in D-cells (259 min), and greater than 300 min in A-cells. These results demonstrate that the transport/prohormone conversion relationships are unique in each of the islet cell types monitored.
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PMID:Simultaneous assessment of prohormone transport and processing in four separate islet cell types: a combined autoradiographic and biochemical study. 290 25

We have studied the viscosity dependence of the acrylamide quenching of the fluorescence on the internal tryptophan residues in cod parvalbumin and ribonuclease T1, as well as the model systems. N-acetyl-L-tryptophanamide and glucagon. For the latter systems, the apparent rate constant, kq(app), for acrylamide quenching shows a typical diffusion-limited behavior. For parvalbumin and ribonuclease T1, however, the viscosity dependence of kq(app) is quite different. There is little change in the kq(app) values on increasing the bulk viscosity from 1 to 10 cP (by addition of glycerol), but a further increase from 10 to 100 cP results in a significant reduction in the kq(app). Both an unfolding mechanism and a quencher penetration mechanism are considered to explain the results. Only the penetration mechanism is found to be consistent, and our data are interpreted as indicating that the rate-limiting step for quenching goes from being that of diffusion through the protein matrix, at low viscosity, to diffusion through the bulk solvent, at high viscosity. By also considering the Kramers' relationship in fitting our data, we are able to obtain insight regarding the coupling between internal fluctuations in the structure of the protein and motion of the bulk solvent. For parvalbumin and ribonuclease T1, the internal dynamics are found to be very weakly coupled to the bulk.
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PMID:Viscosity dependence of the solute quenching of the tryptophanyl fluorescence of proteins. 310 4

We compared the acute effects of intragastric administration of protein and carbohydrate on tryptophan and 5-hydroxytryptamine (5HT) in rat brain, pineal, intestine, and pancreas. Protein decreased and carbohydrate increased brain indoles relative to water-infused controls. These effects were due to competition between the large neutral amino acids for entry into the brain. This competition does not exist in the pineal. The macronutrients had no effect on pineal tryptophan metabolism. In the intestine, protein resulted in higher tryptophan levels as compared to controls, owing to absorption of tryptophan in the protein. However intestinal 5HT levels were influenced by factors other than precursor availability. Pancreatic indoles were affected in a similar manner to the brain indoles. Competition between the large neutral amino acids for entry into the pancreas was also indicated by the finding that valine administration lowered brain and pancreatic tryptophan, but not the levels in the intestine and pineal. It remains to be seen whether the decrease in pancreatic 5HT after a protein meal and the increase after carbohydrate modulate the release of insulin and glucagon.
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PMID:Effects of carbohydrate and protein administration on rat tryptophan and 5-hydroxytryptamine: differential effects on the brain, intestine, pineal, and pancreas. 316 82

Eight men were given 2 casein meals, one with and one without a supplement of arginine and glycine, to measure the effect on plasma amino acids, insulin and glucagon. Supplementation resulted in increased levels of plasma glucagon, glycine and arginine, a tendency to decreased insulin and significantly lower insulin/glucagon ratio, tryptophan and tyrosine. The data suggest that insulin and glucagon, which control cholesterol metabolism, respond to dietary and postprandial plasma amino acid levels of arginine and glycine.
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PMID:Testing a mechanism of control in human cholesterol metabolism: relation of arginine and glycine to insulin and glucagon. 328 27

The fluorescence detected circular dichroism (FDCD) spectra of dansyl-leucine are reported. These spectra were obtained with the use of an unique device. FDCD, circular dichroism (CD) and absorption spectra of dansyl-leucine are combined to calculate CD spectra of the dansyl group in the given environment. A new method for determination of the secondary protein structure from the CD spectra taking into account the contribution of tryptophan residues is proposed. This contribution is defined from FDCD. The secondary structure of glucagon and human serum albumin, all containing a single, fluorescent tryptophan, were analysed. A good correspondence between these results and those reported for glucagon structure were found, while the usual method (without determination on tryptophan contribution) leads to unsatisfactory results.
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PMID:[Applicability of the fluorescence-detected circular dichroism method for the determination of the secondary structure of glucagon and albumin]. 337 88

In F344 rats bearing transplantable 3-methylcholanthrene (CAS: 56-49-5)-induced sarcomas, plasma concentrations of immunoreactive insulin were decreased following the development of mild or severe anorexia. Plasma levels of immunoreactive glucagon and lactate were elevated in severely anorectic tumor-bearing (TB) rats, while plasma glucose concentrations remained normal. Both groups of TB rats exhibited decreased plasma levels of serine, glutamine, citrulline, and tryptophan and increased concentrations of alanine. Plasma levels of proline and phenylalanine were also elevated in the severely anorectic TB rats. In a second experiment, 7 daily treatments with insulin corrected the anorexia for 6 days and increased body weights of TB rats. Plasma concentrations of lactate and immunoreactive glucagon were decreased, and the abnormal plasma concentrations of glutamine, proline, analine, and phenylalanine were altered toward normal following the insulin treatments. Therefore, these data are consistent with insulin treatments benefiting the TB host by increasing feeding, increasing body weight, reducing tumor glycolysis and metabolism, reducing gluconeogenesis, and reducing host catabolism, while not stimulating tumor growth. Thus insulin therapy may have potential benefits in cancer treatment by shifting glucose metabolism toward the host and away from the tumor.
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PMID:Reversal of tumor-induced biochemical abnormalities by insulin treatment in rats. 352 58

The effects of sub-lethal doses of endotoxin on plasma glucose, glucagon, insulin, glucocorticoids and non-esterified fatty acids (NEFA) were determined in rats. Endotoxin did not change the plasma concentration of glucocorticoids, but blocked the effects of elevated glucocorticoid hormone concentrations on both plasma glucose and hepatic tryptophan dioxygenase activity. Endotoxin increased the plasma concentrations of glucose, glucagon and insulin in rats with basal glucocorticoid concentrations, and changed the observed relationships between glucose, glucagon and insulin in a manner consistent with an increased sensitivity of glucagon secretion to lowered glucose concentrations. At the highest dose of endotoxin used, 20 mg/kg over 6 hr, a substantial decrease (greater than 7-fold) in the insulin/glucagon ratio provides evidence for changes in basal (as opposed to hormone-stimulated) glucose production and/or utilisation in vivo.
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PMID:The roles of glucagon, insulin and glucocorticoid hormones in the effects of sublethal doses of endotoxin on glucose homeostasis in rats. 353 7

The tryptophan (Trp) rotational dynamics and the secondary structure of the peptide hormones adrenocorticotropin-(1-24) [ACTH(1-24)]--the fully active N-terminal fragment of adrenocorticotropin-(1-39)--and glucagon were studied in aqueous solutions and in reverse micelles of sodium bis(2-ethylhexyl) sulfosuccinate (AOT)/water/isooctane, a system selected to mimic the membrane-water interface. In aqueous solutions, the total fluorescence intensity decays of their single Trp residue [Trp-9 and Trp-25 for ACTH(1-24) and glucagon, respectively] are multiexponential. This is also the case for ACTH(5-10), a fragment of the adrenocorticotropin "message" region. Time-resolved fluorescence anisotropy data evidence a high degree of rotational freedom of the single Trp residue. Transfer of these peptides from water to the aqueous core of reverse micelles induces severe restrictions of the Trp internal motion and of its local environment. The results indicate that the Trp-9 residue in ACTH(1-24 is maintained in the close neighborhood of the water-AOT molecular interface where the water molecules are strongly immobilized. By contrast, the Trp residues in ACTH(5-10) and glucagon are likely to be located closer to the center of the micellar aqueous core where the water molecules are in a more mobile state. Furthermore, the above location of Trp can be extended to the peptide chains themselves as evidenced by the overall correlation time values of the peptide-containing micelles. Nevertheless, in all peptides, the indole ring remains susceptible to oxidation by N-bromosuccinimide. Circular dichroism measurements evidence the induction in glucagon of alpha-helices remaining unaffected by the micellar water content. Conversely, beta-sheet structures are favored in ACTH(1-24) at low water-to-surfactant molar ratios (w0) but are disrupted by subsequent additions of water. These results are discussed in terms of the possible role of the micellar interfaces in selecting the preferred peptide dynamical conformation(s)
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PMID:Conformational aspects and rotational dynamics of synthetic adrenocorticotropin-(1-24) and glucagon in reverse micelles. 367 84

The effects on the conceptus of persistently decreased maternal plasma amino acid concentrations were studied in pregnant rats by the infusion of glucagon (0.21 mg/day) to the mother from day 14 to 20 of gestation with a subcutaneous, osmotically driven minipump. Controls received diluent. The experimental animals either had normal caloric intake and weight gain, or diminished caloric intake with no weight gain. Both experimental groups exhibited a decrease in plasma total amino acid concentration of approximately 50%. Maternal plasma glucose and insulin concentrations were unaffected except for slight decreases in the low weight gain group. At cesarean section on day 20, fetal weight was unaffected in the normal weight gain group, while the low weight gain animals exhibited intrauterine growth retardation. Fetal plasma glucose and insulin concentrations were unaffected. Despite the marked decrease in maternal plasma total amino acid concentration, fetal plasma total amino acid concentration was unaffected. Individual plasma amino acid concentrations in the normal weight gain mothers and fetuses revealed a spectrum of changes. Some maternal amino acids were decreased by more than 60% (alpha-aminobutyric acid, asparagine, threonine, glutamine, alanine) while others were unaffected (tyrosine, tryptophan, phenylalanine, histidine). In general, amino acids that were decreased in the mother exhibited no change or a lesser decrease in fetal plasma concentration, while those that were unaffected in the mothers showed increased fetal concentrations. Fetuses from the low weight gain mothers had plasma amino acid profiles that were similar to those of the normal weight gain mothers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preserved fetal plasma amino acid concentrations in the presence of maternal hypoaminoacidemia. 379

The canine gastric mucosa has previously been shown to contain considerable amounts of a polypeptide with the immunologic and physicochemical characteristics and biologic activity of glucagon (IRG3500). Using mucosal pieces that remained viable for at least 8 h, we have demonstrated that IRG3500 is synthesized in this extrapancreatic tissue. Gel filtration and electrophoresis of extracts of mucosal pieces incubated with 3H-tryptophan, 3H-leucine, or 35S-methionine revealed small amounts of labeled, newly synthesized gastric IRG3500. No labeling of gastric IRG3500 was observed when the mucosa was incubated with 3H-proline, an amino acid not found in glucagon, in the presence of cycloheximide, or in isolated rat hepatocytes. Small amounts of newly synthesized IRG3500 were specifically immunoprecipitated by C-terminally directed glucagon antiserum gamma globulins. The rate of gastric IRG3500 biosynthesis in vitro was apparently unchanged in mucosal pieces from pancreatectomized dogs and unaffected by increased glucose or glucose lack during incubations. Thus we have provided evidence that a hormone of the endocrine pancreas can be synthesized in extrapancreatic tissues.
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PMID:Biosynthesis of glucagon (IRG3500) in canine gastric mucosa. 388 May 48


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