Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of the islet amyloid polypeptide (IAPP) gene within the endocrine pancreas and its correlation with insular neuroendocrine peptide localization were investigated in the rat. In situ hybridization with a 35S-labelled IAPP-mRNA specific oligonucleotide probe was combined with immunocytochemistry. In situ hybridization alone showed strong autoradiographic labelling of the pancreatic islets. In situ hybridization combined with immunocytochemistry for IAPP, revealed labelling of the IAPP-immunoreactive cells. However, when in situ hybridization was combined with immunocytochemistry for proinsulin, we noted a lack of proinsulin immunoreactivity in some peripherally located autoradiographically labelled islet cells. Furthermore, combination of in situ hybridization and immunocytochemistry for somatostatin showed autoradiographic labelling of somatostatin cells to a varying degree. This was further confirmed by showing cellular co-localization of IAPP and somatostatin by immunocytochemical double staining. We conclude that IAPP is mainly synthesized in insulin cells. Additionally, a subpopulation of the somatostatin cells is capable of IAPP synthesis. This may account for the relatively small reduction in the content of IAPP-mRNA in islets compared to the marked reduction of insulin mRNA after streptozotocin-induced diabetes in rats as previously reported.
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PMID:Islet amyloid polypeptide gene expression in the endocrine pancreas of the rat: a combined in situ hybridization and immunocytochemical study. 790 97

The effect of rat amylin on acid gastric secretion in the pylorus-ligated, unanesthetized rat system (Shay test) was examined. Amylin administered peripherally (2.5, 5, 10, 40, 100, or 160 micrograms/kg, SC) or intracerebroventricularly (1.5, 2.7, or 5 micrograms/rat, ICV) decreased acid gastric secretion in a dose-dependent manner. Central administration of amylin gave a stronger suppression of gastric secretion than peripheral injection. In addition, ICV-injected amylin inhibited insulin-stimulated acid gastric secretion and was effective in suppressing acid gastric secretion in rats depleted of somatostatin by pretreatment with cysteamine. This study suggests that amylin may participate in the central regulation of acid gastric secretion and indicates a possible biological function of amylin as a gastrointestinal peptide.
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PMID:Amylin given by central and peripheral routes inhibits acid gastric secretion. 793 48

Novel monoclonal antibodies to human chromogranin A (CgA) and chromogranin B (CgB) were used to investigate the presence of immunoreactive (-IR) elements in the alimentary tract of the green frog Rana esculenta. Numerous CgA-IR and a few CgB-IR endocrine cells were found within the gut mucosa, from the oesophagus to the cloaca, with some local differences in density. Co-localization studies demonstrated that they were co-stored in almost all the serotonin-IR, the amylin-IR or islet amyloid polypeptide-IR cells and in the peptide tyrosine tyrosine-IR cells located proximal to the pylorus, but not in those located in more caudal tracts. No other co-localization was demonstrated; substances investigated included somatostatin, substance P, gastrin/cholecystokinin, glucagon, glycentin, bombesin, secretin and neurotensin. CgA-IR and CgB-IR cells nearly always displayed argyrophilia with the Grimelius silver method.
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PMID:Immunohistochemical localization of chromogranin A and B in the endocrine cells of the alimentary tract of the green frog, Rana esculenta. 808 25

The GI tract is one of nature's great pharmacies. Most, if not all, biologically active peptides can be found there, and it is quite likely that others remain to be discovered. Our ability to exploit this resource has expanded considerably over the past two decades. Advances in analytical techniques have allowed investigators to rapidly isolate and purify new compounds from tissue extracts. Sequencing and de novo synthesis of newly discovered peptides are now routine, and the structural modifications required to alter activity and tailor a compound to a particular use are easily made. A number of gastrointestinal peptides or their analogues for use in clinical studies are available from commercial sources (see Table 7). Somatostatin is the first gut peptide to successfully complete development and yield a pharmaceutical compound with a broad range of action. Several of the peptides discussed in this article have similar potential. TRH stands out as a candidate because of its effectiveness in the treatment of experimental spinal cord injury and a variety of shock states. Such a broad range of action in critical fields may justify the intensive development required to yield potent, long-acting, and highly specific analogues. Similarly, the antimetastatic and immunostimulant properties of the enkephalins offer promise for new therapies in the treatment of AIDS, ARC, and cancer. Studies with amylin may lead to new and more precise regimens of blood sugar control in insulin-dependent diabetics and could in turn, prevent some of the worst long-term effects of the disease. The development of effective intranasal forms of GHRH could spare children with GH-GHRH deficiency the distress of repeated injections and help to prevent excessive GH blood levels. Secretin, glucagon, or CGRP might be used one day in cardiovascular emergencies, and VIP or its analogues could prove effective in the treatment of asthma. Although preliminary results with many of these peptides are encouraging, further progress will require the development of standardized experimental models and a more rigorous approach to experimental design. Many of the studies reported here suffered from small patient numbers, a narrow or nonexistent range of doses, or the use of only one or two dosing regimens. Lack of objective criteria for determining the level of response, e.g., in studies of mental illness or degenerative diseases, and the ethical problems of withholding treatment from some patients to establish proper controls further hamper research in this area. If the questions of efficacy and safety are to be resolved, thorough, well-planned trials will be required.
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PMID:Therapeutic uses of gastrointestinal peptides. 812 75

The aim of this work was to simultaneously study the secretion of islet amyloid polypeptide (IAPP) and insulin from isolated rat pancreatic islets in vitro. For examination of stimulated beta-cells, nutrient secretagogues (16.7 mM glucose, 10 mM leucine + 2 mM glutamine), phosphodiesterase inhibition (5 mM theophylline), a sulphonylurea (0.5 microgram/ml glipizide), a non-nutrient amino acid (10 mM arginine), cholinergic stimulation (0.1 mM carbamylcholine) and insulinotropic peptides (0.1 microM vasoactive intestinal polypeptide and 0.1 microM glucagon), were used. For beta-cell suppression glucose phosphorylation inhibition (10 mM mannoheptulose), depletion of extracellular calcium, activation of the ATP-regulated K(+)-channel (0.5 mM diazoxide), adrenoreceptor stimulation (3 microM adrenaline), paracrine modulation (0.1 microM somatostatin), short-term treatment with a selective beta-cytotoxin (1.1 and 2.2 mM streptozotocin) and long-term treatment with a cytokine (25 U/ml interleukin-1 beta), were studied. The compounds with known effects on insulin secretion exerted their expected actions and this was paralleled by similar relative changes, with a possible exception for glucagon, in the IAPP secretion. The ratio of IAPP/insulin released did not change significantly under any of the tested experimental conditions, except for a slight increase following carbamylcholine stimulation. On a molar basis approx. 1% of IAPP was released when compared with insulin. These results are consistent with the hypothesis that the regulation of IAPP secretion from beta-cells of isolated rat pancreatic islets is essentially regulated by the same mechanisms as insulin secretion.
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PMID:Cosecretion of islet amyloid polypeptide (IAPP) and insulin from isolated rat pancreatic islets following stimulation or inhibition of beta-cell function. 835 1

Nine human exocrine pancreatic adenocarcinomas were examined by serial sectioning and double- and triple-labeled immunohistochemical techniques with antibodies against chromogranin A, insulin, islet amyloid polypeptide, glucagon, somatostatin, pancreatic polypeptide, serotonin, pancreastatin, and neuron-specific enolase. The results were correlated with the stage of the disease, histologic characteristics of the tumors, and survival of the patients. Cells immunoreactive with most or all of the antibodies were found in all nine cases. Abnormal co-location of some hormones in the same cell and the lack of normal co-location of other hormones were found. Endocrine cells also were identified in the invasive regions of the cancer, including perineural spaces. Abnormality in the production and release of the peptide was indicated not only in the endocrine cells of exocrine cancer, but also in the islets near the cancer. Patients whose cancer contained many endocrine cells seemed to survive longer than those with tumors containing fewer endocrine cells. The overall data suggested that the observed abnormalities may contribute to the impaired glucose tolerance found in six of these patients.
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PMID:Endocrine aspects of exocrine cancer of the pancreas. Their patterns and suggested biologic significance. 837 30

Islet amyloid polypeptide (IAPP) is a 37-amino acid residue polypeptide, originally isolated from the pancreatic amyloid deposits of patients with type II diabetes mellitus. Subsequently, IAPP was found to be colocalised with insulin in beta-cell secretory granules of the normal mammalian pancreas. Recently, IAPP has been reported to inhibit glucose-stimulated insulin release from isolated rat islets and to be released in response to glucose and arginine. To investigate further the regulation of IAPP release from the islet, we used a previously developed specific radioimmunoassay for IAPP and measured IAPP secretion from isolated rat islets of Langerhans. Release of IAPP-like immunoreactivity (-LI) was stimulated by glucose: 3.3 +/- 0.3, 3.9 +/- 0.3, and 11.1 +/- 1.5 (n = 5, mean +/- SEM) fmol/islet/60 min at 2, 7, and 20 mM, respectively. Carbachol (0.1 mM) increased the release of IAPP-LI at the lower glucose concentrations: 8.1 +/- 0.9, 8.7 +/- 0.6, and 11.7 +/- 1.8 fmol/islet/60 m in at 2, 7, and 20 mM glucose. Somatostatin (1 microM) suppressed glucose-stimulated IAPP-LI release (17.5 +/- 1.5 vs. 5.1 +/- 0.5 fmol/islet/60 min). Chromatographic characterisation of the IAPP-LI released into the incubation medium revealed two immunoreactive forms: The major peak (74% of the total IAPP-LI) corresponded to synthetic IAPP-37, while a smaller form, comprising 26% IAPP-LI, eluted later. In acid extracts of islets, all (> 95%) immunoreactivity co-eluted with the synthetic IAPP.
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PMID:Molecular form of islet amyloid polypeptide (amylin) released from isolated rat islets of Langerhans. 846 Jan

The effects of intracerebroventricular (i.c.v.) or intracarotid (i.a.) administration of amylin (AMY) on growth hormone (GH) release induced by GH-releasing hormone (GHRH) were examined in conscious male rats. Amylin (25 ng-5 micrograms/rat, i.c.v. or 10 micrograms/rat, i.a.) was administered 10 min before GHRH (2 micrograms/kg, i.a.). I.c.v. administration of AMY dose-dependently inhibited GH secretion induced by GHRH but when given peripherally, AMY did not modify the GH response to GHRH. Amylin (10(-8)-10(-6) M) had no direct effect on the rat anterior pituitary in vitro either alone or when incubated with GHRH. To characterize the mechanism(s) involved in vivo in the inhibition of GH by AMY, we examined, at first, the effects of AMY on GHRH-induced GH release in rats depleted of somatostatin by pretreatment (4 h before) with cysteamine (300 mg/kg s.c.). The inhibitory activity of AMY on GH secretion elicited by GHRH seems to be independent of hypothalamic somatostatin; in fact, AMY was still active in rats treated with cysteamine. In addition, we examined the effects of i.c.v. AMY administration on clonidine (CLO)-induced GH secretion and on dopamine and noradrenaline content in the brain, since it is known that GHRH is a stimulus sensitive to changes in central catecholaminergic activity. The failure of AMY to affect GH secretion induced by activation of postsynaptic alpha 2-receptors by CLO and the finding that the peptide decreased noradrenaline content in the hypothalamus and striatum, indicates that AMY may inhibit GH release by interfering with the facilitatory influence of the catecholaminergic system on GH secretion.
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PMID:Inhibitory effect of amylin on growth hormone responsiveness to growth-hormone-releasing hormone in the rat. 853 70

Amylin is a peptide containing 37 amino acids that is mainly expressed in pancreatic B-cells and cosecreted with insulin. It is the major component of the islet amyloid typically found in non-insulin-dependent diabetes mellitus. The amylin mRNA is present in RNA isolated from lung, and amylin receptors have been detected in lung membranes. Recently, amylin was shown to be a potent stimulator of airway mucus secretion. In this study, we characterized the site of amylin expression in rat trachea using a highly specific antiserum and the functional interaction of amylin with somatostatin-14 in mucus secreting cells. Amylin-like immunoreactivity is present in epithelial cells of submucous gland acini. The expression pattern varies, since some acini showed strong staining while others were negative. In addition, some columnar cells of the tracheal lining epithelium are strongly stained. Amylin applied submucosally is a potent stimulator of airway mucus secretion. Somatostatin inhibits this effect. Amylin may influence airway mucus secretion by paracrine and endocrine mechanisms, and our data suggest that amylin and somatostatin belong to the increasing number of peptides that are known to influence airway function.
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PMID:Amylin immunoreactivity in the rat trachea and characterization of the interaction of amylin and somatostatin on airway mucus secretion. 857 4

A rare insulin-immunoreactive neuroendocrine tumor of the duodenum in a 54 year old male is reported. The incidentally identified tumor was located on the anterior free wall of the duodenal bulb and measured approximately 6 mm in diameter. Uncomplicated endoscopic resection of the tumor was carried out. The lesion exhibited classic histologic features of insulinoma of the beta-islet cell type with stromal amyloid deposition. In addition to positive reactivities of chromogranin A, neuron-specific enolase, synaptophysin, Leu 7 (CD57), cystatin C, CA15-3 and cytokeratin, the non-argyrophilic tumor cells were strongly immunoreactive for insulin and C-peptide. The stromal amyloid was clearly labeled for amylin. A few cells were stained for somatostatin, whereas other hormones were negative. Interestingly, a few isolated insulin-positive cells were identified in the non-neoplastic duodenal mucosa in the proximity of the tumor. Immunoelectron microscopy using paraffin sections disclosed insulin-immunoreactive secretory granules in the cytoplasm. The patient exhibited no signs or symptoms of hypoglycemia. Serum insulin levels were not measured prior to resection. No tumors were demonstrated in the pancreas. Magnetic resonance imaging revealed a 1 cm asymptomatic pituitary mass, in association with moderately elevated serum prolactin levels. The patient is currently being followed up in the outpatient clinic.
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PMID:Aberrant insulinoma of the duodenal bulb. 858 Nov 56


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