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)

Secretin is a 27-amino acid gastrointestinal hormone that stimulates the secretion of bicarbonate-rich pancreatic fluid. We isolated and analyzed the coding region of the gene for the rat secretin precursor. The entire coding region spans 692 base pairs and is divided into four regions corresponding to the signal peptide and NH2-terminal peptide, the secretin peptide and processing signal sequences, a part of the COOH-terminal peptide, and the remainder of the COOH-terminal peptide, which are interrupted by three short introns (81, 105, and 104 base pairs). The organization is similar to those of the genes for other members of the secretin family, glucagon and VIP/PHI-27 precursors, supporting the assumption that the genes for the secretin family peptide precursors originated from a common ancestral gene. We also demonstrated that the secretin precursor gene is widely expressed in the brain and in the hypophysis. The regional expression pattern of the secretin precursor gene in the brain is quite different from those of the glucagon and VIP/PHI-27 precursor genes. The secretin precursor gene is highly expressed in the medulla oblongata and pons of the brain and the hypophysis, the expression levels of which are comparable to those in the duodenum. The secretin precursor mRNA in the brain and the hypophysis has the same coding sequence as that in the duodenum, indicating that secretin in the brain and the hypophysis is produced from the same secretin precursor protein as that in the duodenum. This is the first evidence to be reported that the secretin precursor gene is definitely expressed in the brain.
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PMID:The secretin precursor gene. Structure of the coding region and expression in the brain. 206 29

Vasoactive intestinal peptide (VIP) is a neuropeptide having a wide range of effects on a large number of tissues. To gain insight into the role VIP plays in retinal function, VIP receptors in bovine retinal membranes were analyzed in competition binding assays and by affinity labeling studies and compared to VIP receptors in rat liver membranes. In both membrane preparations, high affinity VIP binding sites (KD approximately 1 nM) were detected. Secretin and glucagon, each having close structural homology to VIP, were found to have negligible effects on [125I]VIP binding in retina. In contrast, secretin (KD = 70 nM) was modestly effective in inhibiting [125I]VIP binding to rat liver membranes. Affinity labeling analysis revealed a VIP binding site of 59 kDa in both bovine retinal and rat liver membranes. Digestion of affinity-labeled receptor proteins with endoglycosidase F generated final cleavage products of approx. 45 kDa for both receptors. These results indicate that the retina expresses a high affinity, highly selective VIP receptor thereby supporting a specific function for VIP in this tissue.
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PMID:Characterization of vasoactive intestinal peptide receptors in retina. 216 29

We have demonstrated the existence of two types of hormone-responsive adenylate cyclase in the isolated perfused rat liver. One, less abundant, is linked to glycogenolysis and the other is not. Glucagon stimulates mainly the glycogenolysis-linked fraction and, to a lesser extent, the fraction which is not linked to glycogenolysis. The suppressive effect of insulin is specific for the glucagon-responsive adenylate cyclase and is inhibited by 3-isobutyl-1-methylxanthine (IBMX). However, this mechanism can explain only partly the ability of insulin to suppress glycogenolysis, and is not observed when cAMP is increased sufficiently by glucagon. Secretin-responsive adenylate cyclase is not linked to glycogenolysis and is suppressed specifically by oxymetazoline. The capacity of this suppressive effect is large and not inhibited by IBMX. These results suggest that there is a functional compartmentalization of cAMP within the hepatocyte or among hepatocytes.
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PMID:Two types of hormone-responsive adenylate cyclase in the rat liver. 244 65

Subcellular fractionation of liver homogenates from treated rats was carried out in order to study the mechanism of action of the gastrointestinal polypeptides on glucoronidation. Rats were treated for 90 min with an intravenous infusion of secretin (0.4 cU/h/100 g body weight), glucagon (100 micrograms/h/100 g body weight) and vasoactive intestinal polypeptide (VIP) (300 ng/h/100 g body weight); controls were sham-treated rats. For comparison, another group of animals was treated with a daily injection of phenobarbitone (10 mg/kg), a well-established enzyme inducer. Treatment with the different polypeptides produced minor changes in the subcellular localization of the enzyme. The bulk of activity was always recovered in the microsomal fraction, as identified by both differential centrifugation and the enrichment in specific activity of glucose-6-phosphatase, esterase and NADPH-cytochrome c reductase. Secretin produced a specific increase of bilirubin glucuronidation, more evident in all nuclear fractions. Glucagon increased both bilirubin and p-nitrophenol glucuronidation in all subcellular fractions. VIP had a selective action on p-nitrophenol conjugation of similar extent in nuclear and microsomal fractions. The type of changes observed is suggestive of physicochemical modifications occurring into the cell, perhaps at the membrane environment of different organelles, able to modify the overall conjugation of different substrates by the cell.
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PMID:Subcellular localization of UDP-glucuronyltransferase by differential centrifugation. Changes produced by pretreatment of rats with secretin, glucagon, vasoactive intestinal polypeptide and phenobarbitone. 249 35

Tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, is subject to regulation by the cAMP as well as the calcium and cGMP second messenger systems. Treatment of intact rat PC12 cells with neuropeptides including secretin and vasoactive intestinal polypeptide (VIP) stimulated tyrosine hydroxylase activity 2 to 3-fold in vitro. Secretin (EC50 = 10 nM) was about 3 orders of magnitude more potent than VIP (EC50 = 3 microM). A combination of several protease inhibitors failed to enhance the potency of either peptide. Other members of the secretin family including glucagon and peptide histidine isoleucine (PHI) stimulated tyrosine hydroxylase activity to a lesser extent. Somatostatin, which is not homologous to secretin, was ineffective. The maximal response of tyrosine hydroxylase activation to 1 microM secretin occurred within 6-15 sec. Secretin, VIP, and forskolin also enhanced tyrosine hydroxylase activity (3,4-dihydroxyphenylalanine production) in intact cells, as determined by high performance liquid chromatography and electrochemical detection. Secretin, VIP, PHI, and glucagon increased the levels of cAMP in PC12 cells more than 10-fold, as determined by radioimmunoassay. We also demonstrated that cAMP is released from the cells into the incubation medium following secretin treatment. Secretin and VIP treatment also enhanced the activity of cAMP-dependent protein kinase in a concentration-dependent fashion, as measured subsequently in vitro. Based on the greater potency of secretin in comparison with VIP, PHI, and glucagon, we suggest that the PC12 cells contain a secretin-preferring receptor that increases cAMP levels and brings about an activation of tyrosine hydroxylase activity through the stimulation of cAMP-dependent protein kinase.
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PMID:Regulation of tyrosine hydroxylase activity in rat PC12 cells by neuropeptides of the secretin family. 257 21

The growth of cultured epithelium like cells from human normal embryonic intestine was studied in response to various hormones using a method that quantifies the number of cells by the amount of dye that they bind after fixation. Gastrin and neurotensin in the pg/ml range and higher caused small increases in cell growth. Glucagon and VIP were stimulatory in the low ng/ml range, whereas somatostatin and bombesin had no effect at the lower concentrations but were stimulatory at the highest concentration tested (10 and 100 ng/ml respectively). Secretin and pancreozymin (cholecystokinin) seemed to be ineffective.
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PMID:Effects of gastrointestinal hormones on the growth of human intestinal epithelial cells in vitro. 261 94

Glucagon, vasoactive intestinal polypeptide and secretin are strong stimulators of lipolysis in adipose tissue from laboratory animals. Yet, in human adipose tissue these data could not be confirmed under comparable experimental conditions. Using pH stat titration, an advanced in vitro test system for evaluating lipolysis, it was possible to demonstrate lipolytic activity for glucagon down to a concentration of 10(-8) mol/l. This is comparable to the minimal effective doses in rat adipose tissue and corresponds to the effect of equimolar concentrations of noradrenaline in man. Secretin with an amino acid sequence very similar to glucagon was not lipolytically active, while VIP stimulated free fatty acid release in a concentration of 10(-6) mol/l. Since the minimal effective dose of glucagon is only 30 times greater than the plasma levels a physiological significance of these finding may be suggested. The lipolytic activity of VIP seems to be only of pharmacological interest.
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PMID:Human glucagon and vasoactive intestinal polypeptide (VIP) stimulate free fatty acid release from human adipose tissue in vitro. 275 73

Enteroendocrine cells immunoreactive for gastrin, bovine pancreatic polypeptide (BPP), glucagon (glicentin), 5-hydroxytryptamine (5-HT), somatostatin, secretin, motilin, gastric inhibitory peptide (GIP) and cholecystokinin (CCK) are scattered throughout the small intestinal epithelium of the newborn opossum and in all later postnatal stages examined. The number of BPP- and glucagon-immunoreactive cells is relatively high in the newborn and rapidly decreases until only occasional cells are present after the first postnatal week. Cells immunoreactive for GIP, CCK, 5-HT, motilin, gastrin and secretin increase in number with development. Secretin-, motilin-, CCK- and GIP-immunoreactive cells generally are concentrated proximally in the small intestine and as they increase in number, differentiate in more distal regions. The number of gastrin-immunoreactive cells actually decreases just prior to weaning but then increases at and after, weaning. Neurotensin-immunoreactive cells are unusual in that they do not appear until about the 74th postnatal day and then are first encountered in the distal small intestine. As development progresses they increase in number and appear in the more proximal regions. Cells immunoreactive for 5-HT at first increase but then decrease sharply at weaning only to increase markedly again after this time. In contrast, somatostatin-immunoreactive cells gradually decrease in number until weaning then dramatically increase. If the total number of enteroendocrine cells in the small intestine is considered, there is a gradual decrease from birth until weaning when a dramatic increase occurs. Cells immunoreactive for neurotensin, 5-HT and somatostatin are also found in the intestinal epithelium of the developing colon and caecum. Somatostatin- and 5-HT-immunoreactive cells are found throughout the colon in the newborn whereas neurotensin-immunoreactive cells, although observed initially in the proximal colon, do not form a significant population until weaning and then are concentrated distally.
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PMID:Enteroendocrine cells in the developing opossum small intestine and colon. 280 25

The ability of members of the secretin-glucagon family of peptides to modulate the responses of mouse lymphoid cells stimulated with Concanavalin A (Con A), Lipopolysaccharide (LPS) and alloantigens was determined. It was observed that vasoactive intestinal peptide (VIP) and peptide having NH2-terminal histidine and COOH-terminal Isoleucine (PHI) inhibited the incorporation of 3H-methyl-thymidine by cells stimulated with Con A (55% inhibition) or alloantigen-bearing cells (40% inhibition). Secretin was approximately 10,000 less effective as an immunomodulator. Other members of the neuropeptide family, including glucagon and gastric inhibitory peptide, were ineffective in affecting mitogenesis elicited by Con A (20% inhibition). Lipopolysaccharide stimulated spleen cells were refractory to modulation by all members of the secretin-glucagon family of peptides (less than 5% modulation). The inhibition measured was concentration dependent over the range of 10(-6) to 10(-16) M. A peptide fragment of VIP encompassing amino acid residues 10-28, although capable of modulating in vitro responses, was 30-50% less effective than intact VIP. In addition, a VIP specific binding assay for mouse lymphoid cells was described. The binding of 125I-VIP to lymph node cells was rapid, saturable and reversible. Apparent equilibrium was reached within 15 minutes and nonspecific binding, measured as 125I-VIP binding in the presence of an excess (2 x 10(-7) M) of native VIP, did not exceed 25% of the total binding. In competitive experiments using VIP related peptides, PHI but not gastric inhibitory peptide, glucagon or secretin was able to significantly inhibit 125I-VIP binding. PHI had only one-eighth of the competitive capacity of native VIP. Scatchard analyses indicated the existence of a single class of high affinity receptors on lymph node cells (KD = 3.46 nM; 26,000 sites/cell). 125I-VIP specific binding to purified T cells (14%) was markedly higher than to B cells (3% binding). Thymocytes bound less than 2% of the label and had relatively few VIP binding sites (8,000) as compared with purified T cells (45,000 sites/cell). There was variability in the ability of various T cells tumors and functional T cell clones to bind 125I-VIP. The role of VIP as a physiological modulator of T cell activation is discussed.
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PMID:Analysis of the immunomodulatory properties of the secretin-glucagon family of peptides on mouse lymphoid cell functions and the demonstration of specific receptors on T cells. 283 22

Secretin and glucagon potentiate glucose-induced insulin release. We have compared the effects of secretin and glucagon with that of four hybrid molecules of the two hormones on insulin release and formation of cyclic AMP (cAMP) in isolated mouse pancreatic islets. All six peptides potentiated the release of insulin at 10 mM D-glucose, and their effects were indistinguishable with respect to the dynamics of release, dose-response relationship, and glucose dependency. However, measurements of cAMP accumulation in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (10(-4) M) showed that the fold increase compared with glucose alone had the following ranking order: secretin = [Tyr10, Tyr13]-secretin 1.6 less than [Tyr10, Tyr13, Trp25]secretin 1.8 less than glucagon 1.9 less than [Asp3, Glu9, Arg12]glucagon 2.3 = [Asp3, Glu9]glucagon. These results suggest that despite similar potentiating effects of secretin and glucagon on glucose-induced insulin release, their modes of action may be different.
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PMID:Insulin release by glucagon and secretin: studies with secretin-glucagon hybrids. 283 12


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