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)

The glucagon superfamily includes the polypeptides glucagon, secretin, vasoactive inhibitory peptide (VIP), gastric inhibitory peptide and growth hormone-releasing factor (GHRF). Complementary DNA clones which encode the precursors to glucagon, VIP and GHRF have been isolated. Although the sizes and sequences of preproglucagon, prepro VIP and preproGHRF are distinct, the structural organization of the three precursors is similar. Each has a signal peptide, an NH2-terminal peptide and one, two or three peptides whose sequences are related to glucagon. Prepro VIP and preproGHRF also have a COOH-terminal peptide. The sequences of two different anglerfish preproglucagon molecules have been determined and they contain the sequences of glucagon and a related peptide. In contrast, hamster, cow and rat preproglucagon contain the sequences of glucagon and two related peptides. Human and rat prepro VIP contain the sequences of VIP and the related peptide PHM/PHI-27. Human and rat preproGHRF contain the sequence of only one peptide related to glucagon, i.e., GHRF. The genes for both preproglucagon and preproGHRF have been isolated. Their exon-intron organization indicates that each exon encodes a functionally distinct region of the precursor and mRNA.
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PMID:The glucagon superfamily: precursor structure and gene organization. 309 95

Vasoactive Intestinal Peptide (VIP), originally considered to be a gut hormone, has recently been found to increase estrogen and progesterone production by ovarian granulosa and luteal cells. Because several studies indicate that granulosa cells and oocytes are capable of producing plasminogen activators, we have studied the effects of VIP on plasminogen activator activity in cultured granulosa cells and cumulus-oocyte complexes collected from the ovaries of hypophysectomized, estrogen-treated immature rats. Using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) followed by a fibrin overlay technique to assess plasminogen activator activity, we observed that treatment with VIP stimulated the secretion of tissue-type plasminogen activator (tPA), but not urinary-type plasminogen activator (uPA), in a dose-dependent manner by cultured granulosa cells as well as by cumulus-oocyte complexes, but not by denuded oocytes. However, preparation of cumulus-free oocytes from cumulus-oocyte complexes which had previously been treated with VIP indicated substantial increases in tPA activity within the oocyte. The actions of VIP on tPA activity in granulosa cells were specific, because other closely related peptides (PHM-27 and glucagon) were ineffective. These effects of VIP, in addition to the previously observed effects on steroidogenesis, suggest that VIP may be an important regulator of ovarian function.
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PMID:Vasoactive intestinal peptide stimulates plasminogen activator activity by cultured rat granulosa cells and cumulus-oocyte complexes. 310 37

By immunohistochemistry it was found that VIP- and peptide HI/peptide HM (PHI/PHM)-like immunoreactivity occurred in autonomic neurons in the human pancreas. Antisera against both VIP and PHI/PHM reacted with neuronal cells in local ganglia and these ganglia also contained PHI/PHM- and VIP-immunoreactive fibre plexuses. VIP- and PHI/PHM-positive fibres were also seen close to the Langerhans' islets. In addition, PHI/PHM- but not VIP-like immunoreactivity was observed in the endocrine cells often located in the periphery of the islets. The nature of these PHI/PHM-positive cells remains to be established. I.v. infusion of VIP at constant rates of 300 and 900 pmol/kg X h for 30 min in 6 healthy volunteers resulted in plateau values of 102 +/- 26 and 291 +/- 25 pM, respectively. These levels of VIP which are above those found in the circulation under physiological conditions stimulated secretion of insulin, C-peptide and pancreatic glucagon dose-dependently. On the contrary prolonged (60 min) infusion of PHM in doses resulting in plasma levels up to 1340 +/- 405 pM had no effect on pancreatic hormone secretion. These findings suggest that VIP is a likely neurotransmitter in the control of endocrine pancreatic secretion while PHM has a less prominent role, if any.
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PMID:Occurrence of VIP and peptide HM in human pancreas and their influence on pancreatic endocrine secretion in man. 330 16

The human vasoactive intestinal polypeptide (VIP) precursor contains a sequence, a peptide with an N-terminal histidine and C-terminal methionine (PHM), which is 93% homologous to the porcine intestinal peptide, (PHI) a peptide having N-terminal histidine and C-terminal isoleucine amide, suggesting that PHI could be a product of the porcine VIP precursor. If so, VIP-producing nerves would be expected to produce and release PHI in addition to VIP. We studied this in the pig pancreas. By immunohistochemistry, we identified nerve cell bodies in local ganglia and nerve fibers that were both PHI and VIP immunoreactive, innervating exocrine as well as endocrine structures. During electrical stimulation of the vagus nerve supply to the isolated perfused pig pancreas, a synchronous and approximately equimolar release of immunoreactive PHI and VIP was observed. Both responses were abolished by hexamethonium and could be copied by cholinergic agonists. Infusions of PHI and VIP at 10(-9) M stimulated the exocrine secretion of fluid and bicarbonate, and the effect of a combination of the two peptides was additive. In addition, both peptides stimulated insulin as well as glucagon secretion. By gel chromatography the VIP immunoreactivity in the venous effluent corresponded precisely to synthetic VIP, but only 24% of the PHI immunoreactivity corresponded to synthetic PHI; a larger peptide (mol wt 5,000-7,000) was responsible for the majority. The biological activity of this component is unknown. The results suggest that both VIP and PHI, released from intrapancreatic nerve fibers, participate in the parasympathetic control of pancreatic secretion.
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PMID:VIP and PHI in the pig pancreas: coexistence, corelease, and cooperative effects. 354 23

Vasoactive intestinal polypeptide (VIP) is a 28-amino-acid hormone produced primarily by neural tissues. The amino acid sequence of VIP is similar to that of a number of gastrointestinal hormones, including glucagon and secretin. VIP is synthesized as part of a polyprotein, pre-proVIP, which generates, in addition to VIP, an additional bioactive peptide known as PHM. As a first step toward understanding the molecular basis of pre-proVIP gene expression, we have isolated the pre-proVIP gene and have determined its structure. The gene is approximately 9 kb long and is interrupted by six introns which appear to divide the gene into functional domains. One of the introns occurs within the 3'-untranslated region of the gene.
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PMID:Structure of the human vasoactive intestinal polypeptide gene. 389 57

The correspondence schemes for the amino acid sequence families from different animal species for two superfamilies of protein-peptide hormones and their precursors, i.e., proinsulin-IGF-prorelaxin and proglucagon-pro (PHM-VIP)-prosomatocrinin, were constructed. These schemes were used for the local intra- and interfamilial comparison of the sequences; the average profiles of hypothetical secondary structure of individual sites of these sequences according to Chow and Fasman were obtained, and the profiles of their physico-chemical properties (e. g., hydrophobicity and volume of side amino acid radicals) were computed. An analysis of the profiles obtained demonstrated that despite the apparent similarity of the tertiary structure of IGF and relaxin, on the one hand, and of insulin, on the other, the latter is devoid of the insulin-like receptor (effector) site, whereas in the case of IGF, this site is modified by additional links of the peptide chain. Based on the reciprocal comparison of prosomatocrinin with proglucagon and pro (PHM-VIP), it was assumed that the C-terminal fragment of prosomatocrinin separated from somatocrinin by a single arginine residue is a second glucagon-like peptide in the precursor molecule, which apparently possesses a biological activity.
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PMID:[Computer bank of amino-acid sequences of protein hormones. Analysis of evolutionary, conformational and physico-chemical properties of the individual sites of sequences in superfamilies of proinsulin and proglucagon]. 391 76

Vasoactive intestinal polypeptide (VIP), a 28-amino acid peptide originally isolated from porcine duodenum, is present not only in gastrointestinal tissues but also in neural tissues, possibly as a neurotransmitter, and exhibits a wide range of biological actions (for example, relaxation of smooth muscle, stimulation of intestinal water and electrolyte secretion and release of insulin, glucagon and several anterior pituitary hormones). As the structure of porcine and bovine VIP shows several similarities to those of mammalian glucagon, secretin and gastric inhibitory peptide (GIP), VIP is considered to be a member of the glucagon-secretin family. Recently, we have found that VIP is synthesized from a precursor, pro-VIP (molecular weight (Mr) 17,500), in human neuroblastoma cells and that the primary translation product of the mRNA encoding VIP is prepro-VIP (Mr 20,000). In an attempt to elucidate the primary structure of the precursor, we have now cloned the DNA sequence complementary to the mRNA coding for human VIP and analysed the nucleotide sequence. The entire amino acid sequence of the precursor, deduced from the nucleotide sequence, indicates that the precursor protein contains not only VIP but also a novel peptide of 27 amino acids. The peptide, designated PHM-27, differs by only 2 amino acids from PHI-27, a peptide recently isolated from porcine intestine, and is also closely related in sequence to VIP.
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PMID:Human preprovasoactive intestinal polypeptide contains a novel PHI-27-like peptide, PHM-27. 657 96

A receptor capable of recognizing VIP-related peptides with unusual functional characteristics and selectivity profile was characterized on human IGR37 melanoma cells. When using either [125I]VIP or [125I]N-AcPACAP27 as a tracer, PACAP38 had the highest affinity, while PACAP27, VIP, helodermin, GRF and the VIP fragment VIP10-28 showed the same low affinity. Moreover, this receptor did not recognize PHM, PHV, helospectin, secretin, GIP, glucagon and glucagon-like peptide-1(7-36). Surprisingly, none of the peptides significantly stimulated the cAMP production. By covalent crosslinking, the receptor was shown to have a M(r) = 60,500.
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PMID:A receptor for VIP-related peptides with an unusual selectivity profile on the melanoma cell line IGR37. 770 17

The effect of vasoactive intestinal peptide (VIP) on stimulation of adenylyl cyclase in fetal human nonpigmented ciliary epithelial (NPE) and pigmented ciliary epithelial (CPE) cells was studied. 1 microM VIP elicited a 5-10 fold increase in intracellular cAMP in NPE cells from three fetal donors, but caused little or no response in CPE from two fetal donors and other ocular cell types employed as controls. Appearance of cAMP in the extracellular medium was stimulated in NPE but not in CPE in response to VIP. Both NPE and CPE gave similar cAMP responses (8-13 fold) to the beta-adrenergic agonist, isoproterenol. Binding studies of [125I]VIP to intact NPE and CPE revealed that VIP bound to NPE cells at a high affinity site (KD = .33 nM and a low affinity site (KD = 16 nM), whereas VIP bound to CPE cells only at the low affinity site (KD = 18 nM). In NPE cells, VIP stimulated cAMP formation with an EC50 of approximately 0.6-1 nM, similar to the high affinity binding site KD, with maximal stimulation at 10 nM. Four peptides with various degrees of sequence homology to VIP were also studied. Of these, PHM and PHI stimulated cAMP with EC50s of 50 and 300 nM, respectively, while secretin and glucagon stimulated only at concentrations above 0.1 microM. These results suggest that in fetal human ciliary epithelium, as in rabbit ciliary epithelium (Mittag et al., J Pharm Exp Ther 241: 230, [1987]), VIP stimulation of adenylyl cyclase is a characteristic of NPE but not CPE cells.
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PMID:High affinity vasoactive intestinal peptide receptors on fetal human nonpigmented ciliary epithelial cells. 803 89

We studied the distribution of the enzymes that are involved in the post-translational alpha-amidation of regulatory peptides in human endocrine pancreas, using immunocytochemical methods for light and electron microscopy. Immunoreactivity for the two enzymes involved, peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL), was located in the periphery of the islets of Langerhans and in ductal endocrine cells. Staining of reverse-face serial sections demonstrated that these immunoreactivities co-localize with glucagon but not with pancreatic polypeptide (PP), insulin, or somatostatin. Double immunogold staining for electron microscopy confirmed the previous results and revealed a different localization for each enzyme inside the secretory granule: PHM is present in the central core of the glucagon-containing granules, whereas PAL is predominantly located near the granule membrane. The existence of an amidated peptide, GLP1, in the A-cells explains the presence of peptidylglycine alpha-amidating monooxygenase enzymes (PAM) in these cells. The absence of the enzymes in the PR-cells raises the possibility that a different form of amidating enzyme may be involved in the post-translational processing of this peptide.
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PMID:Immunocytochemical localization of peptidylglycine alpha-amidating monooxygenase enzymes (PAM) in human endocrine pancreas. 809 86


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