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)

Glucagon was acylated at position 12 using conditions favoring reaction with the epsilon-amino group of lysine. The N epsilon-acetyl, N epsilon-hexanoyl, and N epsilon-decanoyl derivatives were prepared and purified. Secondary structure as measured by circular dichroism was lower in all derivatives than in glucagon, both in 95% methanol and in 25 mM sodium dodecyl sulfate at pH 2 and pH 12. N epsilon-Acetyl glucagon was less active than the native hormone in a radioreceptor assay and higher concentrations of this derivative were required to stimulate the adenylate cyclase activity of rat liver plasma membranes. The maximal extent of cyclase activation by this derivative was less than that found with the native hormone. N epsilon-Hexanoyl glucagon and N epsilon-decanoyl glucagon had greater activity than N epsilon-acetyl glucagon in receptor binding as well as in adenylate cyclase activation, although these two derivatives were not as active as the native hormone. N epsilon-hexanoyl glucagon and N epsilon-decanoyl glucagon were more potent in receptor binding than in adenylate cyclase activation. From these results it appears that the positive charge of the epsilon-amino groups may have a specific role in obtaining maximal biological activity, while the acyl groups contribute to the nonspecific hydrophobic interactions between the hormone and its receptor. In addition, a possible relationship between stabilization of the amphipathic helix in solution and the activity of these and other N epsilon-derivatives of glucagon is discussed.
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PMID:The role of nonspecific hydrophobic interactions in the biological activity of N epsilon-acyl derivatives of glucagon. Studies of conformation, receptor binding, and adenylate cyclase activation. 628 64

Acylation of the alpha- and epsilon-amino groups of histidine-1 and lysine-12 in glucagon with citraconic anhydride resulted in the formation of amide bonds which displayed different stabilities to hydrolysis under mild acid conditions. Treatment of N alpha,epsilon-dicitraconyl glucagon at pH 4.0 and room temperature regenerated the free epsilon-amino group within 16 h, while the citraconyl-alpha-amino group was stable. N alpha-Citraconyl glucagon was purified by anion-exchange chromatography and was a weak partial agonist in stimulating adenylate cyclase in rat liver plasma membranes. The derivative exhibited 1% of the biological potency and 35-40% of the maximal stimulation of glucagon. Binding affinity to plasma membranes was also reduced, but not to as great an extent as adenylate cyclase activity. Removal of the alpha-citraconyl group by treatment with 10 mM HCl at 40 degrees C restored full potency and stimulation to glucagon. These results suggest that the N-terminal histidine of glucagon is involved in both binding to plasma membranes and transduction of the signal to adenylate cyclase.
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PMID:Differential acid stabilities of citraconylated amino groups of glucagon. Preparation of N alpha-citraconyl glucagon and evaluation of its biological properties. 629 17

V1 vasopressin, angiotensin, alpha-adrenergic, and glucagon receptors in liver were studied on membrane fractions prepared from two groups of jerboas ( Jaculus orientalis) given dry or water-enriched diets for periods of 4 to 7 weeks, and from rats acutely treated with pharmacological amounts of arginine-vasopressin (AVP) or (1-deamino-8-D-arginine)-vasopressin (dDAVP). Tritiated (8-lysine)-vasopressin ([3H]vasopressin), tritiated (1-asparagine-5-valine)-angiotensin II ([3H]angiotensin II), tritiated dihydroergocryptine ([3H] DHEC ), and iodinated glucagon ([125I]-glucagon) were used as specific labeled ligands of these receptors. The V1 vasopressin, angiotensin, alpha-adrenergic, and glucagon receptors detected in both groups of jerboas were identical to receptors found in rat liver plasma membranes in regard to the apparent dissociation constants for their respective labeled ligands. Furthermore, vasopressin receptors in jerboa liver membranes discriminated as efficiently as rat liver receptors between the natural neurohypophyseal peptides arginine-vasopressin and lysine-vasopressin on the one hand and the structural analogs (1-deamino-8-D-arginine)-vasopressin and (4-valine-8-D-arginine)-vasopressin on the other. The reduction of antidiuretic hormone (ADH) secretion in jerboas fed a water-enriched diet compared to those on a dry diet (75 +/- 25 pM versus 372 +/- 86 pM) was accompanied by an increase in the number of liver vasopressin receptors (2.79 +/- 0.53 versus 1.25 +/- 0.14 pmol [3H]vasopressin bound/mg protein). The modifications observed were specific for vasopressin receptors, as judged by the maximal binding capacities of [3H]angiotensin II, [3H] DHEC , and [125I]-glucagon, which remained unchanged in jerboas whatever the levels of endogenous circulating ADH. Similarly, administration of pharmacological doses of AVP by iv infusion to rats induced, 2 hr later, a loss of about 50% of V1 liver vasopressin receptors, while the numbers and apparent dissociation constants of angiotensin, alpha-adrenergic, and glucagon liver receptors remained unchanged, and V2 kidney vasopressin receptors were almost desensitized. For V1 liver and V2 kidney vasopressin receptors, the desensitization process was strikingly dependent on the antidiuretic/glycogenolytic activity ratio of the peptide used. Thus, im injection to rats of dDAVP (an analog possessing a very high antidiuretic/glycogenolytic activity ratio) induced, 1 hr later, a total loss of V2 kidney receptors without modification of the number and apparent dissociation constant of V1 liver receptors.
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PMID:Plasma antidiuretic hormone levels and liver vasopressin receptors in the jerboa, Jaculus orientalis, and rat. 632 98

A new cytoplasmic endoprotease, named protease So, was purified to homogeneity from Escherichia coli by conventional procedures with casein as the substrate. Its molecular weight was 140,000 when determined by gel filtration on Sephadex G-200 and 77,000 when estimated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Thus, it appears to be composed of two identical subunits. Protease So had an isoelectric point of 6.4 and a K(m) of 1.4 muM for casein. In addition to casein, it hydrolyzed globin, glucagon, and denatured bovine serum albumin to acid-soluble peptides but did not degrade insulin, native bovine serum albumin, or the "auto alpha" fragment of beta-galactosidase. A variety of commonly used peptide substrates for endoproteases were not hydrolyzed by protease So. It had a broad pH optimum of 6.5 to 8.0. This enzyme is a serine protease, since it was inhibited by diisopropyl fluorophosphate and phenylmethylsulfonyl fluoride. Although it was not inhibited by chelating agents, divalent cations (e.g., Mg(2+)) stabilized its activity. Protease So was sensitive to inhibition by N-tosyl-l-phenylalanine chloromethyl ketone but not by N-tosyl-l-lysine chloromethyl ketone. Neither ATP nor 5'-diphosphate-guanosine-3'-diphosphate affected the rate of casein hydrolysis. Protease So was distinct from the other soluble endoproteases in E. coli (including proteases Do, Re, Mi, Fa, La, Ci, and Pi) in its physical and chemical properties and also differed from the membrane-associated proteases, protease IV and V, and from two amino acid esterases, originally named protease I and II. The physiological function of protease So is presently unknown.
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PMID:Purification and characterization of protease So, a cytoplasmic serine protease in Escherichia coli. 633 74

The intermittent reports concerning metabolic actions of neurohypophysial extracts or hormones encouraged us to study the effect of these substances on the function of the endocrine pancreas. A surprisingly small amount of neural lobe (NL) extract (0.025 NL eq/ml) stimulated a 425% increase in the release of glucagon from islets isolated from the pancreas of the rat. Gel filtration of the extract produced an elution profile of glucagon-releasing activity that was superimposable on the profiles of oxytocin (OT) and arginine vasopressin (AVP). Synthetic OT and AVP each elicited a concentration-dependent stimulation of glucagon release but failed to influence insulin release in medium 199 containing 5.6 mM glucose. They were effective at 0.2 ng/ml (+55%, +50%) and produced a striking increase (five- to sevenfold) at 20 ng/ml. The response to each peptide was greatly diminished in the presence of a higher concentration of glucose (11 mM). The lysine, desamino-, and 1,6-aminosuberyl analogues of vasopressin, vasotocin, and AVP are equipotent peptides, whereas the desglycinamide analogue, pressinoic acid, and angiotensin II were inactive. Injection of AVP (1 microgram iv) produced a rapid increase in peripheral glucagon (+185% in 5 min). The response to injection of OT was less rapid (+105% in 15 min), but in each case elevation of insulin was also observed. Our results provide evidence that OT and AVP can act directly on the endocrine pancreas and may help explain previous reports of metabolic actions of these peptides.
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PMID:Actions of neurohypophysial peptides on pancreatic hormone release. 636 29

Fasting is known to result in marked decreases in urinary urea nitrogen excretion over a 7-day period. In the present studies, changes in whole body protein breakdown rates and in the circulating levels of a number of hormones involved in protein anabolism and catabolism were systematically studied in nine obese subjects after 12 h and after 7 days of fasting. Whole body protein breakdown rates, measured with a primed continuous infusion of L-[U-14C]lysine, were decreased after 7 days of fasting (1.54 +/- 0.12 g/kg . day) compared to those after 12 h of fasting (1.96 +/- 0.10 g/kg . day). Plasma insulin decreased and glucagon increased after 7 days of fasting, resulting in an increased glucagon to insulin molar ratio. Plasma cortisol, urinary free cortisol excretion plasma rT3 levels, and branched chain amino acid levels increased after 7 days of fasting. Serum lysine levels, used for the calculations of whole body protein breakdown rates, were not changed. We conclude: 1) decreased whole body protein breakdown contributes significantly to the decreased nitrogen excretion observed with fasting in obese subjects; and 2) a decrease in circulating levels of free T3 may lead to this adaptive decrease in protein breakdown in fasted obese subjects, since the other hormones measured either did not change or changed in a catabolic direction.
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PMID:Whole body protein breakdown rates and hormonal adaptation in fasted obese subjects. 640 11

Duodenopancreatectomy induces a severe glucagon deficiency and elevated plasma concentrations of alanine, aspartate, glycine, proline, serine, arginine, citrulline, ornithine, phenylalanine and tyrosine. Restoring high physiological plasma glucagon in six such patients by infusing 0.3 mg/24 h of exogenous glucagon reduced significantly (P less than 0.01 or 0.001) the mentioned amino acids (except phenylalanine) and further asparagine, glutamine, methionine and threonine. In six normal subjects the same infusion reduced significantly (P less than 0.05 to 0.001) plasma alanine, asparagine, glutamate, glutamine, glycine, proline, serine, threonine, arginine, ornithine, lysine and tyrosine. However, the effect was significantly (P less than 0.01 or 0.001) less marked for alanine, glutamine, glycine, methionine, serine, threonine and arginine. This particular glucagon sensitivity of duodenopancreatectomized patients suggests that glucagon deficiency is the cause of their hyperaminacidaemia. By contrast, lipoprotein concentrations were virtually unaffected by either glucagon deficiency or its replacement. In the light of the marked hypoaminacidaemia in glucagonoma patients these results attribute to glucagon a major role as a regulator of protein metabolism.
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PMID:Amino acids and lipoproteins in plasma of duodenopancreatectomized patients: effects of glucagon in physiological amounts. 640 37

Male rats were fed for 4 weeks cholesterol-free diets containing proteins from different sources, milk, fish, egg yolk, soybean, rice and peanut. The antihypercholesterolemic effect of vegetable proteins compared to animal proteins was certified. There was a negative correlation (gamma = -0.74) between the serum cholesterol level and the arginine/lysine ratio of dietary protein, suggesting a role of this ratio in determining the serum cholesterol level. In general, the fasting level of circulating insulin was lower whereas that of glucagon was higher on feeding vegetable proteins, thus resulting in a fall of the insulin/glucagon ratio. Changes in the hormonal status may be relevant to the protein effect.
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PMID:Dietary protein-dependent modification of serum cholesterol level in rats. Significance of the arginine/lysine ratio. 642 97

The authors have studied the behavior of Aminoacids (AA), GH, Prolactin (PRL), Insulin (IRI) and blood sugar (BS) after fast intravenous injection of 1 mg of Glucagon (G), in eight normal volunteers. The rise in BS levels soon after G. administration at time 10', 20', 30', 45', 60' prompted to consider the initial phase of the experimental to be under G predominance, although IRI did respond to the infusion with a sharp rise, at time 10', 20', 30', 45'. Glycine, serine, threonine, alanine, lysine, phenylalanine and arginine displayed a significant reduction already at time 10' or 20', when G metabolic effects were dominant, a selective G influence on these AA can be supposed. At time 45' and 60' tyrosine, histidine, methionine, valine, leucine, isoleucine, proline, decreased significantly and glycine, serine, threonine, lysine, alanine, phenylalanine, evidenced further reduction. GH and PRL were not affected by the administration of G.
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PMID:[Behavior of blood amino acids after acute administration of glucagon in humans]. 645 90

The gamma-radiation-induced crosslinking of phenylalanine to glucagon, mediated by OH ., has been shown to involve a limited number of binding sites on the glucagon molecule. Glucagon-phenylalanine adducts were partially separated from other radiolysis products with Sephadex gel filtration; further isolation of adducts was achieved with reverse-phase high-performance liquid chromatography (HPLC). Amino acid analysis of the isolated adducts indicates that the aromatic residues (phenylalanine and tyrosine), basic residues (histidine and lysine), and sulfur-containing residue (methionine) of glucagon are predominantly involved in crosslinking; these are essentially the same residues implicated in glucagon-glucagon crosslinking. Acid hydrolysates and chymotryptic digests of glucagon-phenylalanine adducts were examined with HPLC. The number of amino acid-phenylalanine adducts and also chymotryptic peptides observed was much greater than would have been expected based on the amino acid analysis. This observation is best accounted for by the involvement in crosslinking of radicals formed on the glucagon with more than one possible phenylalanine-derived free radical.
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PMID:Binding-site specificity of the radiolytically induced crosslinking of phenylalanine to glucagon. 671 93


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