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)

Chemical and enzymatic methods have been used to prepare the following series of seven glucagon derivatives modified in the carboxyl-terminal region important for hormone-receptor binding: [des-Asn28,Thr29](homoserine lactone27)glucagon, [des-Asn28,Thr29](homoserine27)glucagon, (S-methyl-Met27)glucagon, [des-Thr29](S-methyl-Met27)-glucagon, [des-Thr29]glucagon,[des-Asn28,Thr29](S-methyl-Met27)glucagon, and [des-Asn28,Thr29]glucagon. The derivatives were isolated in high yield, extensively purified, and chemically characterized. All were found to be full agonists of native glucagon. Binding affinity was evaluated by displacement of mono[125I]iodoglucagon prepared by new methods. Binding and biological activities closely correlated, indicating that most modifications affected the relative binding affinity and relative biological potency of glucagon to a comparable extent. Circular dichroism measured in dilute acid solution resembled that of native glucagon except for [des-Asn28,Thr29]glucagon which displayed increased alpha helicity (25%). All derivatives formed helical structures in 2-chloro-ethanol, although the amount of helicity induced was not closely correlated with biological activity. Binding and biological activities were not affected by removal of Thr-29, though both were reduced 20-fold when Asn-28 was also removed, irrespective of whether homoserine or native methionine remained at the carboxyl terminus. Lactone formation was associated with a further 5-fold reduction in binding affinity but not in activity. Methylation of Met-27 had essentially the same effect as removing the two carboxyl-terminal residues, although the combined effect of both modifications was greater than 100-fold reduction in binding and activity. These findings provide additional insight concerning glucagon structure-function relationships.
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PMID:Glucagon carboxyl-terminal derivatives: preparation, purification, and characterization. 707 63

Chicken secretin has been isolated and its structure determined. It is composed of 27 amino acid residues, and has an amidated C terminus. The amino acid sequence is His-Ser-Asp-Gly-Leu-Phe-Thr-Ser-Glu-Tyr-Ser-Lys-Met-Arg-Gly-Asn-Ala-Gln-Val-Gln -Lys-Phe-Ile-Gln-Asn-Leu-Met-NH2. The structure shows distinct similarities to that of porcine secretin, amino acid identities occur at 14 positions (residues 1-4, 6-9, 11, 14, 17, 20, 24 and 26) but considerable differences are also present among the remaining 13 positions. Chicken secretin further shows a clear structural similarity to the vasoactive intestinal peptide (37% identical positions), the gastric inhibitory peptide (30% identical positions) and to glucagon (52% identical positions), suggesting wide evolutionary and functional relationships.
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PMID:Isolation and characterization of chicken secretin. 746 Sep 28

Immunohistochemical studies have indicated that glucagon-containing cells are present in the intestinal mucosa of the agnathan Petromyzon marinus (sea lamprey) but are absent from the pancreas. Glucagon was isolated from an extract of intestinal tissue taken from specimens of sea lamprey during their parasitic phase. The primary structure of the peptide was established as: His-Ser-Glu-Gly-Thr5-Phe-Thr-Ser-Asp-Tyr10-Ser-Lys-Tyr-Leu- Glu15-Asn-Lys-Gln-Ala-Lys20-Asp-Phe-Val-Arg-Trp25-Leu- Met-Asn-Ala. This amino acid sequence shows 8 substitutions compared with that of mammalian glucagon but, with the exception of the COOH-terminal alanine residue, lamprey gut glucagon contains no structural features that have not been previously seen in glucagons isolated from the pancreata of gnathostomes. The amino acid sequence of lamprey glucagon-like peptide (GLP) demonstrates that the primary structure of this peptide has been less well conserved than that of glucagon. The sequence His-Ala-Asp-Gly-Thr5-Phe-Thr-Asn-Asp-Met10-Thr-Ser-Tyr- Leu-Asp15-Ala-Lys-Ala-Ala-Arg20-Asp-Phe-Val-Ser-Trp25- Leu-Ala-Arg-Ser-Asp30- Lys-Ser shows 16 amino acid substitutions compared with the corresponding region of mammalian GLP-1 and 15 substitutions compared with that of salmon GLP.
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PMID:Primary structures of glucagon and glucagon-like peptide isolated from the intestine of the parasitic phase lamprey Petromyzon marinus. 840 97

The Polypteriformes (bichirs and reedfish) are a family of ray-finned fishes of ancient lineage. Insulin has been isolated from an extract of the pancreas and upper gastrointestinal tract of the bichir Polypterus senegalis and its primary structure established as A-chain: Gly-Ile-Val-Glu-Gln-Cys-Cys-Asp-Thr-Pro10-Cys-Ser- Leu-Tyr-Asp-Leu-Glu-Asn-Tyr-Cys20-Asn: B-chain: Ala-Ala-Asn-Arg-His-Leu-Cys-Gly-Ser-His10-Leu-Val- Glu-Ala-Leu-Tyr-Leu-Val-Cys-Gly20-Asn-Arg-Gly-Phe- Phe-Tyr-Ile-Pro-Ser-Lys30-Met. Despite the fact that Polypterus insulin contains several unusual structural features that are not found in insulins from other jawed fish (Asp at A-8, Thr at A-9, Arg at B-4, Asn at B-21, Ile at B-27, Met at B-31), all the residues in human insulin that are involved in receptor binding, dimerization, and hexamerization have been conserved. A comparison of the structures of insulins from a range of species indicates that Polypterus insulin most closely resembles paddlefish insulin II (seven amino acid substitutions). In contrast, Polypterus glucagon (His-Ser- Gln-Gly-Thr-Phe-Thr-Asn-Asp-Tyr10-Thr-Lys-Tyr- Gln-Asp-Ser-Arg-Arg-Ala-Gln20-Asp-Phe-Val-Gln- Trp-Leu-Met-Ser-Asn) most closely resembles the glucagons from the gar Lepisosteus spatula and the bowfin Amia calva (four amino acid substitutions). The data are consistent with the conclusion based on comparison of morphological characteristics that the Polypterids are the most basal living group of the Actinopterygians with evolutionary connections to both the Acipenserids and the Neopterygians.
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PMID:Purification and structural characterization of insulin and glucagon from the bichir Polypterus senegalis (Actinopterygii: Polypteriformes). 944 26

Insulin and four peptides derived from the posttranslational processing of proglucagon have been isolated in pure form from the pancreas of the cane toad, Bufo marinus. Although Bufo insulin contains 9 amino acid substitutions, compared with human insulin, all those residues that are considered to be involved in receptor-binding and in dimer and hexamer formation have been conserved. Bufo insulin was, however, more potent (4-fold) than human insulin in inhibiting the binding of [125I-Tyr-A14] insulin to the soluble full-length recombinant human insulin receptor, which is probably a consequence of the substitution (Thr --> His) at position A-8. Bufo glucagon was isolated in two molecular forms: glucagon-29 shows only one amino acid substitution (Thr29 --> Ser), compared with human glucagon; and glucagon-36 comprises glucagon-29, extended from its C-terminus by Lys-Arg-Ser-Gly-Gly-Met-Ser. The human proglucagon gene contains one copy of glucagon-like peptide (GLP)-1, a potent insulin secretogogue, and one copy of GLP-2 that is devoid of insulin-releasing activity. In contrast, two proglucagon-derived peptides with 32- and 37-amino acid residues (GLP-32 and GLP-37), displaying greater structural similarity to human GLP-1 than to GLP-2, were isolated from Bufo pancreas. Both peptides produced concentration-dependent increases in insulin release from glucose-responsive rat insulinoma-derived BRIN-BD11 cells. The threshold concentrations producing a significant (P < 0.001) effect were 10(-8) M (GLP-32) and 10(-9) M (GLP-37), and the maximum increase in the rate of insulin release produced by 10(-6) M concentrations of both peptides was approximately 5-fold.
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PMID:Purification and characterization of insulin, glucagon, and two glucagon-like peptides with insulin-releasing activity from the pancreas of the toad, Bufo marinus. 968 94

The wood frog Rana sylvatica utilises glucose, derived from hepatic glycogen, as a cryoprotectant in order to survive freezing during winter hibernation, and glycogenolysis is initiated by hormonal and/or neural stimuli. The primary structure of insulin was determined from R. sylvatica and from two species of freeze-intolerant Ranid frogs R. catesbeiana (American bullfrog) and R. ridibunda (European green frog). All three insulins contain a dipeptide (Lys-Pro) extension to the N-terminus of the A-chain. The amino acid sequences of insulins from R. catesbeiana and R. ridibunda differ by only one residue (Asp for Glu at B21) but R. sylvatica insulin differs from R. catesbeiana insulin at A12 (Thr-->Met), A23 (Asn-->Ser), B5 (Tyr-->His) and B13 (Glu-->Asp). The residue at A23 (corresponding to A21 in human insulin) has been otherwise fully conserved during evolution and the residue at B13 has been strongly conserved in tetrapods. Insulin isolated from specimens of R. sylvatica that had been frozen for 24 h and from control animals that had not been frozen had the same structure, showing that freezing did not alter the pathway of post-translational processing of proinsulin. R. sylvatica glucagon was isolated in two molecular forms. Glucagon-29 was identical to R. catesbeiana glucagon-29 and contains only one amino acid substitution (Thr-->Ser) compared with human glucagon. Glucagon-36 represents glucagon-29 extended from its C-terminus by Lys-Arg-Ser-Gly-Gly-Ile-Ser and is identical to R. catesbeiana glucagon-36. We speculate that selective changes in the structure of the insulin molecule may contribute to the anomalous regulation of glycogen phosphorylase in the wood frog.
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PMID:Freeze tolerance in the wood frog Rana sylvatica is associated with unusual structural features in insulin but not in glucagon. 980 58

Current views on Agnathan phylogeny favor the hypothesis that the genera of holarctic lampreys belong to a single family (Petromyzontidae) and form an interrelated progression in which Petromyzon is near to Ichthomyzon at the base of the phylogenetic tree and Lampetra is the most derived. A stock similar to that of contemporary Ichthomyzon is considered to have given rise to the southern hemisphere lamprey Geotria australis, the sole member of the Geotriidae. In the present study, two molecular forms of glucagon were isolated from an extract of G. australis intestine that differed in structure by six amino acid residues. One form shows two amino acid substitutions (Leu14 --> Met and Ala29 --> Ser) compared with the single molecular form of glucagon isolated from the sea lamprey Petromyzon marinus and the second form shows three substitutions (Asp15 --> Glu, Ser16 --> Ala, Ile24 --> Thr) compared with the single glucagon isolated from the river lamprey Lampetra fluviatilis. As Petromyzon and Lampetra glucagons differ by six amino acid residues, the data suggest that a duplication of the glucagon gene occurred prior to or early in lamprey evolution. Although both genes are strongly expressed in G. australis, the expression of one gene predominates in P. marinus while that of the other gene predominates in L. fluviatilis. Previous work has shown that, in the islet organ of G. australis, preprosomatostatin is processed almost exclusively to somatostatin-33. However, the present study demonstrates that somatostatin-14 is the major molecular form in G. australis intestine with somatostatin-33 present only as a minor component. This result demonstrates a tissue-dependent pathway of posttranslational processing of preprosomatostatin in the Geotria enteropancreatic system.
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PMID:Multiple forms of glucagon and somatostatin isolated from the intestine of the southern-hemisphere lamprey Geotria australis. 1008 30

Insulin and peptides derived from the processing of proglucagon have been isolated from an extract of the pancreas of the South American horned frog, Ceratophrys ornata (Leptodactylidae). Ceratophrys insulin is identical to the insulin previously isolated from the toad, Bufo marinus (Bufonidae). Ceratophrys glucagon was isolated in two molecular forms with 29- and 36-amino acid residues in approximately equal amounts. Glucagon-29 is identical to glucagon from B. marinus and from the bullfrog, Rana catesbeiana (Ranidae) and contains only 1 amino acid substitution (Thr29 --> Ser) compared with glucagon from Xenopus laevis (Pipidae). Glucagon-36 comprises glucagon-29 extended from its C-terminus by Lys-Arg-Ser-Gly-Gly-Met-Ser. This extension is structurally dissimilar to the C-terminal octapeptide of mammalian oxyntomodulin and resembles more closely that found in C-terminally extended glucagons isolated from fish pancreata. Ceratophrys glucagon-like peptide-1 (GLP-1) (His-Ala-Asp-Gly-Thr-Tyr-Gln-Asn-Asp-Val10-Gln-Gln-Phe-Leu-Glu- Glu-Lys-Ala-Ala-Lys20-Glu-Phe-Ile-Asp-Trp-Leu-Ile-Lys-Gly- Lys30-Pro-Lys-Lys-Gln-Arg-Leu-Ser) contains 3 amino acid substitutions compared with the corresponding peptide from B. marinus, 8 substitutions compared with GLP-1 from R. catesbeiana, and between 4 and 11 substitutions compared with the three GLP-1 peptides identified in X. laevis proglucagon. GLP-2 was not identified in the extract of Ceratophrys pancreas. The data indicate that, despite its importance in the regulation of glucose metabolism, the primary structure of GLP-1 has been very poorly conserved during evolution, even among a single order such as the Anura.
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PMID:Insulin and proglucagon-derived peptides from the horned frog, Ceratophrys ornata (Anura:Leptodactylidae). 1037 73

To characterize the endocrine cell types of the pancreas of Rana temporaria, conventional staining, silver impregnation, and immunocytochemical methods for light and electron microscopy have been applied to paraffin, thin and semithin sections, many of them serial pairs. Quantitative data on the frequency and distribution (insular, extrainsular among the exocrine cells, or within the pancreatic ducts) of each endocrine cell type are also reported. Four distinct endocrine cell types have been identified: insulin (B) cells, which are also immunoreactive for [Met]enkephalin; glucagon/PP (A/PP) cells, also immunoreactive for GLP1; somatostatin (D) cells; and a fourth endocrine-like cell type (X cells) of unknown content and function. X cells display characteristic ultrastructure and tinctorial traits but are nonimmunoreactive for all of the 37 antisera tested. The presence of [Met]enkephalin in amphibian pancreatic endocrine cells is now reported for the first time. Almost half (44.9 +/- 7.9) of the total endocrine cell population lies outside the islets, mainly spread among the exocrine cells. Approximately 37.2 +/- 4.6% of the total endocrine cell population was immunoreactive for insulin, 48.8 +/- 6.9% was immunoreactive for glucagon/PP, and 14.0 +/- 4.9% was immunoreactive for somatostatin; 79.2 +/- 6.4% of glucagon/PP cells are found within the exocrine parenchyma, representing the majority (86.4 +/- 4.3%) of extrainsular endocrine component. On the contrary, most B cells (94.2 +/- 2.1%) are located within the islets; 30.8 +/- 12.9% of D cells are found outside the islets.
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PMID:Characterization of pancreatic endocrine cells of the European common frog Rana temporaria. 1076 48

We found a potent hyperglycemic effect of proadrenomedullin N-terminal 20 peptide (PAMP) after intra-third cerebroventricular administration at a dose of 10 nmol in fasted mice. PAMP has four homologous residues with bombesin (BN), a hyperglycemic peptide. PAMP showed affinity for gastrin-releasing peptide preferring receptor (GRP-R) and neuromedin B preferring receptor. The PAMP-induced hyperglycemic effect was inhibited by [D-Phe(6), Leu-NHEt(13), des-Met(14)]-BN (6-14), GRP-R specific antagonist, indicating that the hyperglycemic effect is mediated at least in part via GRP-R. Furthermore, pretreatment of alpha-adrenergic blocker inhibited the PAMP-induced hyperglycemia and hyperglucagonemia, suggesting that the increase of glucagon secretion through alpha-adrenergic activation is involved in this hyperglycemic effect of PAMP.
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PMID:Proadrenomedullin N-terminal 20 peptide (PAMP) elevates blood glucose levels via bombesin receptor in mice. 1081 76


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