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)

TRH is synthesized in the islets of Langerhans and was found in the perfusate of isolated rat pancreas. In the present study, designed to determine the role of endogenous TRH, we first characterized chromatographically the identity of immunoreactive TRH with synthetic pGlu-His-Pro-NH2. Since endogenous TRH secretion may mask the effects of exogenous TRH, we performed, in parallel to dose-response studies, immunoneutralization experiments using anti-TRH serum to neutralize the endogenous TRH secretion from isolated perfused rat pancreas. The data indicate that exogenous TRH enhances basal glucagon secretion; inversely, anti-TRH serum inhibits glucose plus arginine-induced glucagon secretion and produces a concomitant slight inhibition of somatostatin secretion. The present study shows a physiological contribution for endogenous TRH as a local modulator of intraislet hormone regulation; from these observations, we postulate a direct effect of pancreatic TRH on glucagon-containing (alpha) cell secretion, which, in turn, may produce the fluctuation in somatostatin secretion. Local TRH secretion provides a model for positive feedback regulation of glucagon secretion, frequently associated with diabetes.
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PMID:Antithyrotropin-releasing hormone serum inhibits secretion of glucagon from isolated perfused rat pancreas: an experimental model for positive feedback regulation of glucagon secretion. 163 22

1. Localization and pharmacological properties of the vasoactive intestinal polypeptide (VIP) receptors in rat circle of Willis arteries and in the arteries of pial-arachnoid membrane were studied using light microscope autoradiography combined with radioreceptor binding techniques. 2. [125I]-VIP was specifically bound to sections of rat cerebral arteries with a dissociation constant value of 0.5 nM and a binding site density of 80 fmol mg protein-1. Radioreceptor binding experiments revealed that the binding characteristics of [125I]-VIP were consistent with the labelling of specific VIP receptors. The rank order of potency of various substances tested to inhibit [125I]-VIP binding was the following: VIP greater than peptide histidine methionine greater than secretin greater than glucagon. 3. Light microscope autoradiography revealed the localization of [125I]-VIP binding sites in the medial layer of circle of Willis and pial arteries. Quantitative determination of [125I]-VIP binding site density in the different circle of Willis arteries demonstrated a higher accumulation of silver grains in the anterior than in the posterior cerebral arteries. Pial arteries are richer in VIP receptor sites than circle of Willis arteries. 4. These results suggest that the physiological neurogenic vasodilation elicited by VIP on cerebral arteries is mediated by the interaction with specific receptor sites located primarily within cerebral vessels structures involved in the control of cerebrovascular resistances.
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PMID:Vasoactive intestinal polypeptide receptors in rat cerebral vessels: an autoradiographic study. 166 Aug 95

Vasoactive intestinal peptide (VIP) is a neuroendocrine mediator found in the central and peripheral nervous system. Distinct subsets of neural, respiratory, gastrointestinal, and immune cells bear specific high-affinity receptors for VIP, which are associated with a guanine nucleotide-binding (G) protein capable of activating adenylate cyclase. A cDNA clone (GPRN1) encoding the human VIP receptor was identified in libraries prepared from the Nalm 6 line of leukemic pre-B lymphoblasts and the HT-29 line of colon carcinoma cells. The deduced 362-amino acid polypeptide sequence encoded by GPRN1 shares a seven-transmembrane-segment hydropathicity profile with other G protein-coupled receptors. Northern blot analyses identified a 2.7-kilobase transcript of the VIP receptor in Nalm 6 and HT-29 cells as well as in tissues from rat brain, colon, heart, lung, kidney, spleen, and small intestine. COS-6 cells transfected with GPRN1 bound 125I-labeled VIP specifically with a dissociation constant (Kd) of 2.5 nM. VIP--and less effectively secretin, peptide histidine isoleucine (PHI), and glucagon competitively displaced bound 125I-VIP from transfected COS-6 cells, with potencies in the order VIP greater than secretin = PHI much greater than glucagon. VIP stimulated adenylate cyclase activity in stably transfected Chinese hamster ovary K1 cells, inducing a 3-fold increase in the intracellular level of cAMP. When the antisense orientation of the VIP receptor clone was introduced into HT-29 cells, there was a 50% suppression of the specific binding of 125I-VIP and of the VIP-induced increase in cAMP level, relative to untransfected cells. The VIP receptor cloned exhibits less than or equal to 24% homology with other receptors in the same superfamily and thus represents a subset of G protein-coupled receptors for peptide ligands.
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PMID:Cloning and expression of the human vasoactive intestinal peptide receptor. 167 91

An amino-terminal histidyl structure (His1) is characteristic of most peptides in the glucagon superfamily. An assay for His1 peptides performed by amino-terminal amino acid sequencing was used to screen venom from the Gila monster lizard, Heloderma horridum. Two His1 peptides were identified: helospectin and a new His1 peptide that has been named exendin-3 to indicate that it is the third peptide to be found in an exocrine secretion of Heloderma lizards which has endocrine activity, the first two being helospectin (exendin-1) and helodermin (exendin-2). In the lot of H. horridum venom tested, exendin-3 was 5-10-fold more abundant in molar concentration than helospectin. The structure of exendin-3 was analyzed by amino acid sequencing and mass spectrometry. Exendin-3 is a 39-amino acid peptide with a mass of 4200. It contains a carboxyl-terminal amide and has a strong homology with secretin at its amino-terminal 12 amino acids. The complete structure of exendin-3 is His-Ser-Asp-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala- Val-Arg - Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro- Ser- amide. It is 32 and 26% homologous with helospectin and helodermin, respectively. It has greatest homology with glucagon (48%) and human glucagon-like peptide-1 (50%). Exendin-3 (3 microM) stimulated increases in cellular cAMP and amylase release from dispersed guinea pig pancreatic acini.
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PMID:Purification and structure of exendin-3, a new pancreatic secretagogue isolated from Heloderma horridum venom. 170 Jul 85

The levels of 10 regulatory peptides in acid-alcohol extracts of three regions of the small intestine (0-20%, 30-60%, and 70-100%, with respect to distance from the pylorus) have been monitored radioimmunometrically in sham-infected male (6-8 week old) C57 mice and mice given a 5-cysticercoid infection of the rat tapeworm Hymenolepis diminuta and autopsied 10 days postprimary infection and 5 days postsecondary infection (administered 28 days postprimary infection). The regulatory peptides examined were gastrin, gastrin-releasing peptide (GRP), glucagon (= enteroglucagon), motilin, neurotensin (NT), pancreatic polypeptide (PP), peptide histidine isoleucine (PHI), somatostatin (SRIF), substance P (SP), and vasoactive intestinal peptide (VIP). Statistical analyses revealed significant deviations from control values of five of the peptides (enteroglucagon and SP, both elevated; NT, PHI and VIP, all lowered) in intestinal tissue from infected mice; measurement of the same peptides in colonic extracts revealed no significant differences between infected and sham-infected mice. Parallel changes in peptide levels between normal infected and immunosuppressed infected mice were not evident, although elevations in the tissue levels of enteroglucagon and SP were found in infected Wistar rats (normal host). Results are discussed with respect to a peptidergic involvement in the pathology and host immune response to an intestinal tapeworm.
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PMID:Hymenolepis diminuta: changes in the levels of certain intestinal regulatory peptides in infected C57 mice. 171 77

Vasoactive intestinal polypeptide (VIP) is a gut neuroendocrine polypeptide that increases cyclic adenosine monophosphate (cAMP) production in cells with VIP receptors. Some gastrointestinal cancer cells possess functional receptors for VIP; however, the role of VIP in regulation of growth of gastric cancer cells has not been determined. The purpose of this study was to determine whether VIP and other agents that increase cAMP regulate growth of a human gastric cancer cell line (AGS) and whether these agents regulate expression of c-myc proto-oncogene, which is required for cell proliferation. We measured levels of cAMP by radioimmunoassay, and we used Northern blot analysis to examine c-myc messenger RNA expression. Cell-growth studies were carried out in media supplemented with 3% serum, and cells were counted with a Coulter counter. We found that VIP significantly increased cAMP production of AGS cells in a dose-dependent manner, whereas secretin, glucagon, and peptide histidine methionine (PHM) did not stimulate cAMP production. Exogenous cAMP (8-bromo-cAMP) inhibited AGS cell growth in a dose-dependent manner. VIP acted synergistically with either isobutylmethyl-xanthine or forskolin to inhibit AGS cell proliferation. The increased c-myc expression, which was induced by serum, was inhibited by simultaneous treatment with VIP and isobutylmethyl-xanthine. We have found that AGS cells have specific, functional VIP receptors (activation of which are negatively correlated with cell growth) and that the mechanism by which VIP acts to inhibit cell growth appears to be due, in part, to cAMP-dependent regulation of c-myc proto-oncogene expression.
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PMID:Vasoactive intestinal polypeptide inhibits c-myc expression and growth of human gastric carcinoma cells. 171 57

In order to clarify the relationship between the structure and function of glucagon-like peptide (GLP) 1 in the endocrine function of the pancreas, the response of insulin and glucagon to various synthetic GLP-1-related peptides was investigated in anesthetized dogs. GLP-1-related peptides were administered in a dosage of 400 pmol within 10 min into the pancreatic artery during glucose or arginine infusion and the changes in plasma insulin and glucagon in the pancreatic vein were studied. GLP-1 (7-36) and (7-37), as well as glucagon enhanced insulin release during glucose infusion, whereas neither GLP-1 (1-37), (7-20), (6-37) nor (8-37) stimulated insulin release. The administration of GLP-1 (1-37), (7-36) and (7-37) reduced glucagon release during glucose infusion. When arginine was infused, GLP-1 (7-20), (7-36), (7-37), and glucagon enhanced insulin release. In contrast, glucagon release was increased by the administration of GLP-1 (7-20), (8-37), and (7-37). The present study indicates that histidine at the 7th position of GLP-1 is important in eliciting biological action and that only truncated GLP-1 (7-36), (7-37), and (7-20) showed an insulinotropic action as strong as glucagon in dogs. Furthermore, it is suggested that the response of insulin and glucagon to GLP-1-related peptides is dependent on a background condition.
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PMID:The structure-function relationship of GLP-1 related peptides in the endocrine function of the canine pancreas. 180 8

HPLC-purified 125I-labeled vasoactive intestinal peptide (VIP) bound in a specific, saturable, and reversible manner to pancreatic plasma membranes isolated from newborn calves, from milk-fed calves at 28 and 119 days, and from weaned calves at 119 days. A series of VIP analogues, including pituitary adenylate cyclase-activating polypeptide (PACAP), displaced 125I-VIP binding and activated adenylate cyclase in the same order of relative potency: PACAP-38 greater than helodermin greater than VIP, PACAP-27 greater than PHM (human peptide with NH2-terminal histidine and COOH-terminal methionine amide). At maximally effective concentrations, these five peptides produced the same two- to threefold increase of adenylate cyclase activity in pancreatic membranes from newborn and 28-day-old calves, and fourfold in ruminant or preruminant animals at 119 days. The activation constant for PACAP-38 ranged from 0.1 to 0.34 nM throughout the postnatal development. Helospectin I and II were three times less potent than VIP in inhibiting 125I-VIP binding. At concentrations up to 0.1 microM, secretin, rat and human growth hormone-releasing factors, glucagon, oxyntomodulin, the truncated form of glucagon-like peptide-1 lacking the 6 NH2-terminal amino acid sequence (TGLP-1), GLP-2, gastric inhibitory peptide, gastrin, CCK, and insulin had no effect on binding. Scatchard plots from 28- and 119-day-old calves were compatible with the presence of two classes of 125I-VIP binding sites: one with a high affinity for VIP and a low binding capacity (Kd = 0.11-0.4 nM, Bmax = 66-174 fmol/mg protein) and the other with a low affinity and high binding capacity. At birth, only one class of binding sites was observed (Kd = 0.4 nM, Bmax = 858 fmol/mg protein). The covalently cross-linked PACAP-preferring 125I-VIP binding site is a glycoprotein of 55 kDa with higher sensitivity to PACAP vs. helodermin and VIP. Our results suggest that calf pancreatic functions might be regulated at an early stage of postnatal development by PACAP receptors linked to cAMP generation.
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PMID:Characterization of binding sites for VIP-related peptides and activation of adenylate cyclase in developing pancreas. 184 91

1. The helospectins are peptides structurally related to helodermin, vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI) and secretin, which all potently stimulate glucagon secretion in the mouse. Therefore, the effects of helospectin I (0.1-0.8 nmol kg-1) on insulin and glucagon secretion under basal conditions and after stimulation with glucose (2.8 mmol kg-1) or the cholinoceptor agonist, carbachol (0.16 mumol kg-1), were examined in vivo in the mouse. 2. Helospectin I potently increased plasma levels of glucagon after its intravenous injection in mice. The increase was observed after only 2 min, and was evident also after 6 min. 3. In contrast, plasma insulin levels were not altered by helospectin I after 2 min, but slightly increased after 6 min. Plasma glucose levels were not altered by the peptide. 4. Carbachol-induced glucagon secretion was markedly potentiated by helospectin I. In contrast, glucose- or carbachol-stimulated insulin secretion was not affected by the peptide. 5. In conclusion, helospectin I markedly stimulates glucagon secretion in the mouse whereas the peptide has no direct action on insulin secretion. This pattern of effect of helospectin I is similar to that previously reported for helodermin, VIP, PHI and secretin in the mouse, i.e., for all peptides belonging to this superfamily of peptides.
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PMID:Effects of helospectin I on insulin and glucagon secretion in the mouse. 185 19

The absolute rates of hormone synthesis and release were determined in purified pancreatic B cells. Newly synthesized proteins were labeled with L-[3,5-3H]tyrosine or L-[2,5-3H]histidine. When medium glucose was less than or equal to 10 mM, the production of insulin exceeded or equaled its release. Raising the glucose levels above 10 mM did not further increase the rate of insulin synthesis (67 +/- 10 fmol/10(3) cells/2 hour) but elevated that of insulin release up to 3-fold the production rates (181 +/- 10 fmol/10(3) cells/2 hour). In the presence of glucagon or of the phorbol ester 12-O-tetradecanoylphorbol 13-acetate the cells also released 3-fold more hormone that they synthesized; release was however reduced to 25% of the rate of production in the presence of epinephrine. It is concluded that glucose as well as hormonal regulators of islet B cells can influence, bi-directionally, the balance between the rates of insulin synthesis and release.
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PMID:Measuring the balance between insulin synthesis and insulin release. 187 37


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