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)

Mammalian glucagon is thought to be highly conserved. Glucagons from pig, cow, human, rat, and hamster have identical amino acid sequences, whereas the amino acid contents of rabbit and camel glucagons are consistent with this 29-amino acid sequence. It had earlier been reported that guinea pig (GP) glucagon contains 40 amino acids. In the current study, glucagon was purified from two GP pancreata by a series of three HPLC steps after acid-alcohol extraction and acetone precipitation. GP glucagon is a 29-amino acid peptide that differs from other mammalian glucagons by substitution of Gln for Asp in position 21, Leu for Val in position 23, Lys for Gln in position 24, Leu for Met in position 27, and Val for Thr in position 29. In view of the marked changes in the COOH-terminal of GP glucagon, receptor binding studies were performed using both rat and GP liver membranes. Labeled synthetic porcine glucagon has similar binding in the two systems and its binding is inhibited to a similar degree by synthetic porcine glucagon, whereas GP glucagon is 10-fold less potent at inhibiting binding in both systems. This suggests that glucagon receptor binding sites in the GP are evolutionarily more conserved than is GP glucagon.
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PMID:Guinea pig glucagon differs from other mammalian glucagons. 395 84

Combination of Fast Atom Bombardment Tandem Mass Spectrometry with Amino Acid Analysis assigns the amino acid sequence of the Manduca sexta adipokinetic hormone as pGlu-Leu-Thr-Phe-Thr-Ser-Ser-Trp-GlyNH2. Similarities and differences with other invertebrate hormones and with mammalian glucagon are discussed.
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PMID:Amino acid sequence of Manduca sexta adipokinetic hormone elucidated by combined fast atom bombardment (FAB)/tandem mass spectrometry. 407 73

The administration of glucagon to rats causes a marked increase in the phosphorylation of a specific serine residue in lysine-rich (f1) histone of liver during a one-hour period following the administration of the hormone. It is proposed that histone phosphorylation is the mechanism by which glucagon, and perhaps other hormones whose actions are mediated by adenosine 3',5'-cyclic phosphate (cyclic AMP), induce RNA synthesis in target tissues. The incorporation of (32)P-phosphate into lysine-rich histone is determined by isolation of a tryptic peptide which contains the phosphorylated serine residue. This peptide is identical to the major tryptic phosphopeptide obtained from lysine-rich histone after phosphorylation in vitro by a purified cyclic AMP-dependent liver histone kinase preparation; the partial sequence Lys-Ala-SerPO(4)(Thr,Ser,Glu,Pro(2),Gly,Val,Ile,Leu)Lys has been determined for the peptide. Hydrocortisone and adrenocorticotrophic hormone do not cause a detectable increase in histone phosphorylation in liver. However, insulin, which like glucagon induces an actinomycin sensitive synthesis of liver enzymes, also causes increased histone phosphorylation.
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PMID:Phosphorylation of liver histone following the administration of glucagon and insulin. 431 47

The effect of 20 L-amino acids upon pancreatic glucagon secretion has been studied in conscious dogs. Each amino acid was administered intravenously over a 15 min period in a dose of 1 mmole/kg of body weight to a group of four or five dogs. Pancreatic glucagon and insulin were measured by radioimmunoassay. 17 of the 20 amino acids caused a substantial increase in plasma glucagon. Asparagine had the most glucagon-stimulating activity (GSA), followed by glycine, phenylalanine, serine, aspartate, cysteine, tryptophan, alanine, glutamate, threonine, glutamine, arginine, ornithine, proline, methionine, lysine, and histidine. Only valine, leucine, and isoleucine failed to stimulate glucagon secretion, and isoleucine may have reduced it. No relationship between glucagon-stimulating activity and insulin-stimulating activity was observed. The amino acids which enter the gluconeogenic pathway as pyruvate and, which are believed to provide most of the amino acid-derived glucose, had a significantly greater GSA than the amino acids which enter as succinyl CoA or as alpha-ketoglutarate. However, pyruvate itself did not stimulate glucagon secretion. The R-chain structure of the amino acid did not appear to be related to its GSA, except that the aliphatic branched chain amino acids, valine, leucine, and isoleucine, were devoid of GSA.
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PMID:Glucagon-stimulating activity of 20 amino acids in dogs. 463 19

Albumin synthesis was measured in the isolated perfused rat liver by using the livers of both well-fed and starved rats. Starvation markedly decreased albumin synthesis. The livers from starved rats were unable to increase synthesis rates after the addition to the perfusates of single amino acids or the addition of both glucagon and tryptophan. Arginine, asparagine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threonine, tryptophan and valine, added together to ten times their normal peripheral blood concentrations, restored synthesis rates to normal. The plasma aminogram (i.e. the relative concentrations, of amino acids) was altered by depriving rats of protein for 48h. The use of blood from the deprived rats as perfusate, instead of normal blood, decreased albumin synthesis rates significantly by livers obtained from well-fed rats. The addition of single amino acids, including the non-metabolizable amino acid, alpha-aminoisobutyric acid, to the above mixture increased albumin synthesis rates to normal values. It is concluded that amino acids play an important role in the control of albumin synthesis and that more than one mechanism is probably involved.
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PMID:The effects of amino acids on albumin synthesis by the isolated perfused rat liver. 465 17

Splanchnic and leg exchange of glucose, lactate, pyruvate, and individual plasma amino acids was studied in diabetics 24 hr after withdrawal of insulin and in healthy controls. Measurements were made in the basal postabsorptive state and during the administration of glucose at a rate of 2 mg/kg per min for 45 min. In the basal state, net splanchnic glucose production did not differ significantly between diabetics and controls. However, splanchnic uptake of alanine and other glycogenic amino acids was 1(1/2)-2 times greater in the diabetics, while lactate and pyruvate uptake was increased by 65-115%. Splanchnic uptake of these glucose precursors could account for 32% of hepatic glucose output in the diabetics, as compared to 20% in the controls. This increase in precursor uptake was a consequence of a two- to threefold increment in fractional extraction of these substrates inasmuch as arterial levels of alanine, glycine, and threonine were reduced in the diabetics, while the levels of the remaining substrates were similar in the two groups. Peripheral output of alanine and other glycogenic amino acids as reflected in arterio-femoral venous differences was similar in both groups. An elevation in arterial valine, leucine, and isoleucine was observed in the diabetics, but could not be accounted for on the basis of alterations in splanchnic or peripheral exchange of these amino acids. Administration of glucose (2 mg/kg per min) for 45 min resulted in an 80% reduction in splanchnic glucose output in controls, but failed to inhibit hepatic glucose release in the diabetics despite a twofold greater increment in arterial glucose levels. In both groups no consistent changes in arterial glucagon were observed during the infusion. It is concluded that in nonketotic diabetics (a) total splanchnic output of glucose is comparable to controls, but the relative contribution of gluconeogenesis may be increased by more than 50%; (b) accelerated splanchnic uptake of glucose precursors is a consequence of increased hepatic extraction of available substrates rather than a result of augmented substrate supply; and (c) the failure of glucose infusion to inhibit hepatic glucose output suggests that the exquisite sensitivity of the liver to the infusion of glucose in normal man is a consequence of glucose-induced insulin secretion.
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PMID:Splanchnic and peripheral glucose and amino acid metabolism in diabetes mellitus. 503 28

Porcine ileal mucosa was homogenized and freeze-thawed in 0.05 M NH4HCO3 + 0.01 M EDTA + 1 mM benzamidine hydrochloride at pH 8.6. Subsequent stepwise precipitation with (NH4)2SO4 followed by fractionation on Sephadex G-50 medium and G-50 fine eluted with alkaline buffer and final fractionation on G-50 superfine in 1.0 M acetic acid yielded a pure protein of 13,000 daltons as determined by sodium dodecyl sulfate electrophoresis. The amino acid composition of the protein has been determined and it contains 126 residues with no tryptophan detectable. Tryptic peptide maps demonstrate that the protein does not contain glucagon and RIA of the peptide did not detect any immunoreactive glucagon or gastrin. The isoelectric point is 6.4. The intact protein is resistant to Edman degradation and the partial N-terminal sequences of two CNBr fragments are: Lys-Arg-Leu-Ala-Leu ...., Glu-Gly-Gly-Thr-Val-Val-Val-Asn-Ser.... The C-terminal residue, alanine was determined using carboxypeptidase Y. The isolated peptide, in the range of 10(-15)-10(-9) M stimulated oxyntic cell hydroxyl ion production in sections of guinea pig gastric fundus. The dose response was linear with biphasic peaks at 10(-14) and 10(-9) M and the maximal response to the peptide was equal to that observed with gastrin. The addition of either atropine (10(-5) M) or cimetidine (10(-5) M) with the peptide (10(-14) M) caused greater than 50% inhibition of oxyntic cell stimulation (P less than 0.005). This peptide is a potent stimulator of the oxyntic cell and its effect is inhibited by muscarinic cholinergic and H2 receptor blockers. Hence, it represents a significant component of the physiological enterooxyntin effect observed in response to intestinal meals.
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PMID:Isolation and partial characterization of an entero-oxyntin from porcine ileum. 609 Jan 3

Specific SRIF(1-14) fragments were synthetized on resin using conventional procedures. Rabbits received subcutaneously peptidyl resins in complete Freund adjuvant emulsion. The presence of antibodies was assessed by immunocytochemical and radioimmunological assays. 1. Peptidyl resins lead to antibodies production; their specificity depends on sequence and molecular configuration of the peptide on the resin. Anti-resin antibodies were not detected. 2. In the brain, SRIF(1-4) (in rat) and SRIF(10-13) (in garden-dormouse) can be demonstrated in neurophysins--positive cells of both paraventricular and supraoptic nucleus, but never in hypothalamic or extrahypothalamic SRIF(1-14)--positive neurophysin negative cells. 3. Endocrine cells of pancreatic islets contain SRIF(6-9) (in man) or SRIF(10-13) (in rat, mouse, garden-dormouse); generally, these cells are not detected by SRIF(1-14) anti-serum. Moreover, SRIF(10-13) positive cells are also detected by specific glucagon antibodies. However, it cannot be concluded that SRIF(10-13) antibodies reveal the common Thr-Phe-Thr-Ser fragment in the entire glucagon molecule. It is postulated that antibodies to several SRIF tetrapeptides reveal molecular fragments provided by the functional cleavage of an hypothetical prohormone or by the inactivation of SRIF(1-14) molecule in target cells.
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PMID:[Preparation of antisera against some sequences of somatostatin synthetized on resin. Application to the immunological detection of somatostatin systems: preliminary results (author's transl)]. 612 35

We have utilized the relative structural simplicity of several short, cyclic, highly active somatostatin analogs in the search for competitive antagonists of somatostatin. During an attempted synthesis of cyclo(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr), catalytic hydrogenation of the protected peptide intermediate unexpectedly gave cyclo [7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(Bzl)] in which the benzyl protecting group on Thr could not be removed even upon prolonged treatment under standard conditions. Injection of this new peptide into the rat completely blocked the inhibitory effects of exogenous somatostatin on GH, insulin, and glucagon release. Indeed, in fasted rats, basal hepatic portal insulin and glucagon levels were significantly increased after analog treatment. Plasma GH levels in Nembutal-anesthetized and stimulated rats were also increased after injection of the analog. These results provide strong evidence that endogenous somatostatin exerts local tonic control of pituitary and pancreatic secretions. The availability of a somatostatin anatagonist should be of considerable value in elucidating the roles of somatostatin in these and many other physiological processes.
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PMID:Somatostatin antagonist analog increases GH, insulin, and glucagon release in the rat. 612 18

Structure-activity studies of the lysine residue in the highly active cyclic hexapeptide somatostatin analog cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe) confirm the importance of the lysine amino group for biological activity through the loss of activity seen on replacement of lysine by ornithine, arginine, histidine and p-amino phenylalanine. Three analogs containing thialysine, gamma- and delta-fluorolysine were equipotent to the parent as inhibitors of insulin, glucagon, and growth hormone release. The pKa's of the amino groups in these equiactive peptides ranged from 8.23-9.4. The lack of a correlation between the basicity of the amino groups and the biological activities suggests that deprotonation is not required for biological activity.
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PMID:Somatostatin analogs which define the role of the lysine-9 amino group. 613 Oct 45


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