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)

In this work we have investigated the effect of serotonin on glucagon release in mouse pancreatic islets isolated by the collagenase technique. Incubation of the islets with serotonin (4 X10(-3)mol/l) was associated with an inhibition of glucagon output both in the basal medium (3.3 mmol/l glucose) and in the presence of arginine (10 mmol/l). The inhibitory effect of serotonin on basal glucagon release was also apparent at concentrations of 2 X10(-3) mol/l, 10(-3)mol/l and 5 X 10(-4) mol/l. Addition of 5-hydroxytrypophan (4 X10(-3) mol/l) to the incubation medium was without effect on basal glucagon output while it significantly reduced arginine-induced glucagon release. In contrast, tryptophan (4 X10(-3) mol/l) provoked glucagon secretion. As inferred from our previous human studies, the present data indicate that serotonin is able to inhibit glucagon secretion. These findings provide further support for the participation of a serotoninergic mechanism in the control of A-cell function.
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PMID:Inhibition of glucagon release by serotonin in mouse pancreatic islets. 33 6

We have evaluated the effect of serotonin (5-HT) and of its biosynthetic precursors 5-Hydroxytryptophan (5-HTP) and tryptophan (TRP) on the release of immunoreactive glucagon (IRG) and insulin (IRI) from isolated islets and pieces of pancrease of the rat. In isolated islets, 5-HT inhibited the IRI response to a high glucose concentration (3.0 mg/ml), without affecting the IRG response to either a low (0.5 mg/ml) or a high glucose concentration; TRP stimulated the IRG and IRI response to the low glucose concentration, while 5-HTP was ineffective. When pieces of pancreas were used, 5-HT and 5-HTP inhibited IRG response to both glucose concentrations, while IRI release was inhibited only by 5-HT. The anti-5-HT agent metergoline enhanced the release of IRG and IRI by pieces of pancreas at both glucose concentrations. The results indicate that exogenous and endogenous 5-HT inhibit basal as well as glucose-mediated IRG and IRI release; that isolated islets are less sensitive than pieces of pancreas to the inhibitory effect of 5-HT and that TRP acts as an amino acid and not as a precursor of 5-HT.
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PMID:Effects of serotonin, of its biosynthetic precursors and of the anti-serotonin agent metergoline on the release of glucagon and insulin from rat pancreas. 35 87

No information is at present available on the mode of SRIF biosynthesis. Since anglerfish pancreatic islet tissue is comprised of approximately 30% D cells, we have examined this tissue for SRIF synthesis . The following known differences in amino acid composition of islet peptides were used advantageously in this study: anglerfish proinsulin: Trp-0, Ile-2, Cys-6; anglerfish glucagon: Trp-1, Ile-0, Cys-0; mammalian SRIF: Trp-1, Ile-0, Cys-2. After incubating islet tissue with [3H]tryptophan and [14C]isoleucine or [35S]cystine for various time periods, proteins were extracted in 2 M acetic acid and desalted by Bio-Gel P-2 gel filtration. P-2 void volume proteins were then subjected to P-10 gel filtration and isolated by polyacrylamide gel electrophoresis (PAGE) at alkaline pH. The predominant amount of the immumoreactive SRIF in the extracts appeared in a peak eluting just before the salt volume on P-10 filtration and migrated slowly toward the cathode during PAGE. The behavior of synthetic SRIF was identical. The anglerfish SRIF immunoreactive peptide could be labeled with Trp and Cys but not Ile during incubations longer than 1 h. The Trp- and Cys-labeled peptide could be bound on columns to which the immunoglobulin fraction of antisera to SRIF had been complexed. Cycloheximide inhibited isotope incorporation into all islet proteins. These results indicate that islet SRIF is synthesized in situ. Moreover, the immunological activity, size, and charge characteristics of anglerfish islet SRIF appear to be similar to those of mammalian hypothalamic SRIF. When islets were subjected to short pulse incubations with labeled Trp and Cys, only peptides eluting in the 7,000-13,000 dalton portion of the filtration eluate became labeled. No appreciable isotope incorporation into SRIF was observed. However, when pulse incubations were followed by incubation in the presence of cycloheximide or excess unlabeled amino acids in isotope-free medium (chase), the incorporation of Trp and Cys into SRIF increased with the length of chase, suggesting the participation of a larger precursor in SRIF synthesis.
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PMID:Somatostatin biosynthesis occurs in pancreatic islets. 36 32

Ultrastructural characteristics as well as secretory and biosynthetic behavior of monolayer pancreatic cell cultures established from 4-day-old C57BL/KsJ misty diabetic (m db/m db) mice have been studied in comparison to normal littermate controls. Hypersecretion of glucagon by alpha-cells from BL/Ks misty diabetic mice after 2 days in vitro was found to precede any hyperfunction of the insulin-secreting beta-cells. The increased level of glucagon-release in BL/Ks cell cultures from diabetic mice was accompanied by a greatly enhanced level of incorporation of [3H]tryptophan into glucagon-like molecules whose specific radioactivity was up to 15-fold higher than that observed in cultures from genetic controls. The finding of an alpha-cell dysfunction in cultures established from preweaning diabetic BL/Ks mice suggests that glucagon could play an early role in shaping the events that culminate in the expression of frank diabetes in this inbred strain.
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PMID:Endocrine pancreatic cells of postnatal "diabetes" (db) mice in cell culture. 39 18

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.
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PMID:[12-Homoarginine]glucagon: synthesis and observations on conformation, biological activity, and copper-mediated peptide cleavage. 42 94

Alterations in insulin and glucagon levels might account for the plasma amino acid imbalance of cirrhotics. In order to verify this hypothesis we evaluated basal insulin, glucagon, branched-chain amino acids, aromatic amino acids, and free tryptophan in 13 controls and 37 cirrhotics divided on the basis of their mental state; in 4 patients the hormonal and amino acid patterns were sequentially studied during various stages of encephalopathy. Glucagon is high in cirrhotics and progressively increases with the worsening of the mental state. Free tryptophan and aromatic amino acids show a similar behavior and significantly correlate with glucagon levels (r = 0.67 and r = 0.81, respectively). On the other hand insulin levels, which are high in cirrhotics without encephalopathy, fall in the presence of deep coma. Insulin did not correlate with any of the plasma amino acids considered. Our data suggest that the catabolic state associated with increased glucagon levels may account for some of the alterations in the plasma amino acid profiles of cirrhotics. Portal-systemic shunting does not seem to be the common cause of both hyperglucagonemia and hyperaminoacidemia. Decreased branched-chain amino acid levels may be related to factors different from those involved in the alterations of carbohydrate homeostasis.
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PMID:Insulin and glucagon levels in liver cirrhosis. Relationship with plasma amino acid imbalance of chronic hepatic encephalopathy. 46 10

Changes in the plasma aminoacid (AA) profile present in hepatic encephalopathy were related to a catabolic state characterized by a reduced insulin/glucagon molar ratio (IRI/IRG). Oral glucose is able to suppress the hyperglucagonemia and further to increase the elevated insulin levels of cirrhotics leading to a rise of IRI/IRG. We evaluated the plasma AAs in ten controls and twelve cirrhotics following the ingestion of oral glucose. At 180 min we demonstrated a similar fall (about 35%) of plasma AAs both in cirrhotics and in controls, with the exception of free tryptophan, which fell more markedly in cirrhotics (about 60%), possibly secondary to the fall in plasma free fatty acids. After the oral glucose load, the levels of aromatic AAs and free tryptophan, as well as the molar ratio free tryptophan/branched-chain + aromatic AAs returned to normal in cirrhotics. High levels of both aromatic AAs and free tryptophan have been implicated in the pathogenesis of hepatic coma. Our data support the hypothesis that the administration of oral glucose might be relevant in the management of cirrhotic patients with hepatic encephalopathy, possibly improving their mental state.
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PMID:Oral glucose in cirrhotics. Effects on plasma aminoacid patterns and the role of insulin and glucagon. 47 83

Glucagon can form amphipathic helices and can interact with dimyristoyl glycerophosphocholine at temperatures below the phase transition leading to a shift in the fluorescence emission maximum of tryptophan from 350 to 338 nm and a 3-fold enhancement of fluorescence intensity as well as a change in the polarization of fluorescence. The circular dichroism properties of the lipid-associated glucagon indicates that it has an increased content of alpha-helix. The phase transition temperature of the lipid as monitored by pyrene excimer fluorescence is not altered by interaction with glucagon although at higher glucagon/lipid ratios a decrease in excimer formation is noted at low temperature. Above the phase transition temperature, the addition of lipid has no effect on the fluorescence emission or circular dichroism of glucagon. Thus this hormone can interact with dimyristoyl glycerophosphocholine and this interaction is stronger below the phase transition temperature than above it.
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PMID:Interaction of glucagon with dimyristoyl glycerophosphocholine. 55 46

Succus entericus from jejunal Thiry-Vella fistulae in fasting conscious dogs was analyzed for amino acids before and after incubation for 15 and 30 min at 38 degrees C in vitro. Total amino acid concentration of succus entericus as collected was about twice that of blood plasma. After incubation, it was increased 76% above control at 15 min and 137% at 30 min. Because succus entericus does not exhibit proteinase activity, and no enzyme or substrate was added before incubation, the increase in amino acid concentration was probably due to hydrolysis of peptides by peptidases normally present in the juice. Volume of secretion and output of amino acids were greatly increased by intravenous administration of glucagon, but the amino acid pattern was quite different from blood plasma. The concentrations of aspartic and glutamic acids were 10- and 5-fold greater than in plasma, and tryptophan was usually undetectable.
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PMID:Possible role of succus entericus in amino aicd homeostasis in the dog. 61 25

Optical detection of magnetic resonance (ODMR) has been employed to examine the homogeneity of the tryptophan environment, both of the isolated residue in solvent, and of tryptophan in glucagon and lysozyme and azurin B (Pseudomonas aeruginosa). From the shifts in the zero-field splittings, we can safely conclude that tryptophan in lysozyme, azurin B, or glucagon does not have the same type of solvent interaction as the free residue. However, by "burning holes" in the OSMR lines, it is evident that the lines in these cases are inhomogeneously broadened. From the relative line widths and hole widths, it appears that ODMR can be used to examine the relative diversity of interactions for a luminescent amino acid in a protein. We have followed the ODMR line characteristics in a progression from free N-acetyl-L-tryptophanamide, to tryptophan in lysozyme, to "denatured" lysozyme, and present evidence that the line widths narrow as the tryptophan residues become less solvent accessible.
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PMID:Triplet state of tryptophan in proteins: the nature of the optically detected magnetic resonance lines. 62 48


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