Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 purpose of the present study was to investigate the regulation of insulin biosynthesis during the perinatal period. The incorporation of [3H]leucine into total immunoreactive insulin (IRI) and into IRI fractions was measured by a specific immunoprecipitation procedure after incubation, extraction, and gel filtration in isolated 3-day-old rat pancreases without prior isolation of islets. IRI fractions were identified by their elution profile, their immunological properties, and their ability to compete with the binding of 125 I-insulin in rat liver plasma membranes. No specific incorporation of [3H]leucine was found in the IRI eluted in the void volume, making it unlikely that this fraction behaves as a precursor of (pro) insulin in this system. In all conditions tested, the incorporation of [3H]leucine was linearly correlated with time. Optimal concentration of glucose (11 mM) activated six- to sevenfold the [3H]leucine incorporation into IRI. Theophylline or N6O2-dibutyryl- (db) cAMP at 1.6 mM glucose significantly increased the [3H]leucine incorporation. Glucose at 16.7 mM further enhanced the effect of both drugs. Contrarily, somatostatin (1-10 mug/ml) inhibits the rate of [3H]leucine incorporation into IRI in the presence of 11 mM glucose; this effect was observed at 5.5 mM glucose and was not modified by any further increase in glucose concentrations up to 27.5 mM. Theophylline or dbcAMP at 10 mM concentration did not reverse the somatostatin inhibitory effect on either insulin biosynthesis or release. Somatostatin also inhibited both processes in isolated islets from the 3-day-old rat pancreas. High Ca++ concentration in the incubation medium reversed the inhibitory effect of somatostatin on glucose-induced insulin biosynthesis as well as release. In both systems the inhibitory effect of somatostatin on insulin biosynthesis and release correlated well. Glipizide (10-100 muM) AND TOLBUTAMIDE (400 MUM) inhibited the stimulatory effect of glucose, dbcAMP, and theophylline on [3H]leucine incorporation into IRI. The concentrations of glipizide that were effective in inhibiting [3H]leucine incorporation into IRI were smaller than those required to inhibit the phosphodiesterase activity in isolated islets of 3-day-old rat pancreas. These data suggest the following conclusions: (a) the role of the cAMP-phosphodiesterase system on insulin biosynthesis is likely to be greater in newborns than in adults; (b) the greater effectiveness of glucose and the cAMP system on insulin biosynthesis than on insulin release might possibly be related to the rapid accumulation of pancreatic IRI which is observed in the perinatal period; (c) somatostatin, by direct interaction with the endocrine tissue, can inhibit glucose and cAMP-induced insulin biosynthesis as well as release; calcium reverses this inhibition; (d) sulfonylureas inhibit insulin biosynthesis in newborn rat pancreas an effect which has to be considered in the use of these agents in human disease.
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PMID:Biosynthesis of proinsulin and insulin in newborn rat pancreas. Interaction of glucose, cyclic AMP, somatostatin, and sulfonylureas on the (3H) leucine incorporation into immunoreactive insulin. 17 41

Scintigraphy with 123I-Tyr-3-octreotide has several major drawbacks as regards its metabolic behavior, its cumbersome preparation and the short physical half-life of the radionuclide. The use of another radiolabeled analog of somatostatin, 111In-DTPA-D-Phe-1-octreotide, has consequently been proposed. DTPA-D-Phe-1-octreotide can be radiolabeled with 111In in an easy single-step procedure. DTPA-D-Phe-1-octreotide is cleared predominantly via the kidneys. Fecal excretion of radioactivity amounts to only a few percent of the administered radioactivity. For the radiation dose to normal tissues, the most important organs are the kidneys, the spleen, the urinary bladder, the liver and the remainder of the body. The calculated effective dose equivalent is 0.08 mSv/MBq. Optimal 111In-DTPA-D-Phe-1-octreotide scintigraphic imaging of various somatostatin receptor-positive tumors was obtained 24 hr after injection. In the six patients studied, tumor localization with 123I-Tyr-3-octreotide and with 111In-DTPA-D-Phe-1-octreotide were found to be similar. However, the normal pituitary is more frequently visualized with the latter radiopharmaceutical. In conclusion, 111In-DTPA-D-Phe-1-octreotide appears to be a sensitive somatostatin receptor-positive tissue-seeking radiopharmaceutical with some remarkable advantages: easy preparation, general availability, appropriate half-life and absence of major interference in the upper abdominal region, because of its renal clearance. Therefore, 111In-DTPA-D-Phe-1-octreotide may be suitable for use in SPECT of the abdomen, which is important in the localization of small endocrine gastroenteropancreatic tumors.
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PMID:Somatostatin receptor scintigraphy with indium-111-DTPA-D-Phe-1-octreotide in man: metabolism, dosimetry and comparison with iodine-123-Tyr-3-octreotide. 134 39

In situ hybridization studies with [32P] and [3H] labelled antisense RNA probes were undertaken to determine optimal methods of tissue fixation, tissue sectioning, and conditions of hybridization, and to compare the relative merits of the two different radioactive labels. The distribution of somatostatin mRNA in neurons of rat brain using a labelled antisense somatostatin RNA probe was employed as a model for these studies. The highest degree of sensitivity for in situ hybridization was obtained using paraformaldehyde fixation and vibratome sectioning. Optimal autoradiographic localization of mRNA was obtained within 7 days using [32P] labelled probes. However, due to the high energy emittance of [32P], precise intracellular localization of hybridization sites was not possible. [3H] labelled RNA probes gave more precise cellular localization but required an average of 18-20 days autoradiographic exposure. The addition of the scintillator, PPO, decreased the exposure time for the localization of [3H] labelled probes to seven days. We also report a method for combined in situ hybridization and immunocytochemistry for the simultaneous localization of somatostatin in mRNA and peptide in individual neurons.
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PMID:In situ hybridization methods for the detection of somatostatin mRNA in tissue sections using antisense RNA probes. 243 82

Specific binding sites for somatostatin have been identified in cytosolic fraction of rabbit kidney (cortex and outer medulla) using 125I-Tyr11-somatostatin. The binding was saturable and reversible, as well as time and temperature dependent. Optimal pH for binding was observed at about 7.4. Scatchard plots were compatible with the existence of two classes of binding sites: a first class with a high affinity (Kd = 40 nM) and a low binding capacity (2.0 pmol somatostatin/mg protein) and a second class with a low affinity (Kd = 222 nM) and a high binding capacity (114.3 pmol somatostatin/mg protein). Vasoactive intestinal peptide, neurotensin, substance P, Leu-enkephalin and vasopressin had practically no effect on somatostatin binding. The properties of these binding sites strongly support the concept that somatostatin could behave as a regulatory peptide on the rabbit kidney.
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PMID:Evidence for somatostatin binding sites in rabbit kidney. 287 91

A 56-year-old woman newly diagnosed as having Zollinger-Ellison syndrome due to a metastatic gastrinoma underwent 24-hour intragastric pH monitoring, serum gastrin (total, G-17 and G-34) measurements, and immunoperoxidase staining of duodenal, antral, and gastric body biopsies for gastrin, somatostatin, and serotonin. Determinations were made while the patient was given different doses of ranitidine, enprostil (a synthetic orally administered prostaglandin E2), or ranitidine plus enprostil. Following are the findings from this single-patient study: Intragastric pH was persistently low but varied in response to food when the patient was given ranitidine. Immunocytochemical staining of antral biopsies obtained before the patient was treated revealed a reduced number of cells containing G-17 and G-34 but an increase in the antral somatostatin-containing D-cells. Treatment with 35 micrograms of enprostil BID plus 300 mg of ranitidine BID for two and 11 weeks was associated with an increased number of duodenal G-cells, a decrease in antral D-cells, and a decrease in the number of antral serotonin-containing cells. Enprostil in a dosage of 35 or 70 micrograms BID had no effect on intragastric pH, but when enprostil was given in combination with ranitidine, postprandial and nocturnal intragastric alkalinity was accentuated along with a return of duodenal and antral G-cells and a loss of the antral D-cell hyperplasia. Optimal pH control was achieved with 300 mg of ranitidine BID; more frequent dosing with ranitidine did not further increase intragastric pH. Both the total serum gastrin concentration and G-17 levels fluctuated in response to meals. The serum concentrations of total gastrin, G-17, and G-34 were reduced with enprostil and with ranitidine.
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PMID:Synergistic interaction between an H2-receptor antagonist and enprostil on 24-hour intragastric pH, serum gastrin concentration, and tissue immunoperoxidase staining for gastrin, somatostatin, and serotonin in a patient with metastatic gastrinoma. 287 26

The glucagonoma syndrome is characterized by a necrolytic migratory erythematous rash, angular stomatitis, painful glossitis, a normochromic normocytic anemia, mild diabetes mellitus, weight loss, a tendency to thrombosis, and neuropsychiatric disturbances. The diagnosis is made by finding a high plasma glucagon concentration in the absence of any other cause, such as renal failure or severe stress. A pancreatic alpha-cell tumor can be identified and stained by immunocytochemistry with glucagon antibodies. Optimal treatment is surgical removal, but approximately 50 percent of the tumors have metastasized by the time of diagnosis. Since the tumor is slow-growing, remission can be obtained by hepatic artery embolization to shrink hepatic secondaries or by shrinkage, in about 10 percent of patients, with the combination chemotherapeutic regimen of 5-fluorouracil and streptozotocin. The rash frequently responds to administration of zinc, a high-protein diet, and control of the diabetes with insulin. Alongside the alpha cell in the islets of Langerhans is the D-cell, which produces somatostatin and may well act physiologically as a paracrine inhibitor of glucagon release. A newly developed, long-acting somatostatin analogue, SMS 201-995, which the patient can self-administer as a subcutaneous injection, has proven effective in suppressing glucagon secretion from glucagonomas and, in some cases, causing remission of clinical symptoms.
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PMID:Glucagonoma syndrome. 288 77

The solubilization of somatostatin receptors from guinea-pig pancreas by different non-denaturing detergents was investigated after stabilization of the receptors by prior binding of 125I-[Tyr11]somatostatin or its analogue 125I-[Leu8,DTrp22,Tyr25]somatostatin 28, to pancreatic plasma membranes. The somatostatin-receptor complexes were solubilized in a high yield by Zwittergent 3-14 (3-[tetradecyldimethylammonio]-1-propanesulfonate), a zwitterionic detergent. Other detergents, digitonin, Triton X-100, Chaps (3-[cholamidopropyldimethylammonio]-1-propanesulfonate) and octyl beta-D-glycopyranoside, achieved only partial solubilization. The recovery of receptor complexes was increased by glycerol. In order to characterize solubilized somatostatin-receptor complexes, membranes receptors were covalently labelled using N-5-azido-2-nitrobenzoyloxysuccinimide as cross-linking reagent before solubilization. Gel filtration chromatography analysis resulted in the identification of a major protein component of apparent Mr = 93,000 which interacted with the two radioligands. In addition, a similar component of Mr = 88,000 was characterized after analysis by SDS-PAGE of membrane receptors covalently cross-linked with 125I-[Leu8,DTrp22,Tyr25]somatostatin 28 by different heterobifunctional reagents: N-5-azido-2-nitrobenzoyloxysuccinimide, N-hydroxysuccinimidyl 4-azidobenzoate, N-succinimidyl 6-(4'-azido-2'-nitrophenylamino)hexanoate. Optimal cross-linking results were obtained with N-5-azido-2-nitrobenzoyloxysuccinimide. The solubilized somatostatin-receptor complex was adsorbed to wheat-germ agglutinin-agarose column and eluted by specific sugars. We concluded that the guinea-pig pancreatic somatostatin receptor in the membrane and in the non-denaturing detergent solution behaves as a protein monomer of apparent Mr approximately 85,000-90,000. The somatostatin receptor is a glycoprotein which contains complex-type carbohydrate chains.
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PMID:Solubilization and characterization of guinea-pig pancreatic somatostatin receptors. 303 26

The hormonal regulation of thyroglobulin synthesis has been studied using two independent clones of the OVNIS 6H cell line. Insulin, hydrocortisone and TSH were able to stimulate thyroglobulin synthesis, whereas transferrin, somatostatin and glycyl-histidyl-lysine were without effect. Insulin stimulated thyroglobulin synthesis without affecting cAMP production. Hydrocortisone, when combined with insulin was a stimulator too; this stimulation was not accompanied by an increase in cAMP. TSH alone was unable to stimulate either cAMP or thyroglobulin synthesis. The stimulatory effect of TSH on thyroglobulin synthesis took place only when combined with insulin or insulin plus hydrocortisone, and was mediated by cAMP. Consequently, insulin and hydrocortisone stimulated thyroglobulin synthesis by cAMP-independent mechanisms, whereas TSH acted via the cAMP system. Forskolin mimicked TSH effects on cAMP and thyroglobulin synthesis. Calf serum inhibited cAMP and thyroglobulin production. Optimal cAMP and thyroglobulin synthesis as well as TSH responsiveness were obtained in serum-free medium supplemented with 5 micrograms/ml insulin, 100 nM hydrocortisone and 1 mU/ml TSH.
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PMID:cAMP dependent and independent regulation of thyroglobulin synthesis by two clones of the OVNIS 6H thyroid cell line. 304 Apr 95

Optimal conditions were sought for the study of GH secretion by cultured normal pituitary cells. Dispersed rat pituitary cells were cultured for 1 week in four different media supplemented with 10% fetal calf serum. Minimal essential medium resulted in high GH content and secretion during a 4-h incubation period, whereas GH secretion was lower (P less than 0.05) for cells cultured in medium 199, Ham's F-10, and RPMI-1640. GH secretion/24 h declined gradually with time. After 2 weeks in culture hormone secretion amounted to 30% of secretion on day 1, but after 3 weeks GH secretion was still measurable. GH recovery during the 3-weeks culture period was more than 600% of the amount initially plated. GH secretion was positively correlated with the bicarbonate concentration between 0.85 and 2.2 g/liter NaHCO3. When pituitary cells were cultured in concentrations varying from 0.5 X 10(5) to 10 X 10(5) cells per dish, GH secretion and content per cell were constant, suggesting that no direct autofeedback occurred in cultures with high cell densities and thus high medium GH. Dexamethasone stimulated GH secretion and content in a dose-dependent way (0.1 nM-10 microM). The stimulatory effect of 100 nM dexamethasone occurred within 24-48 h. After 7 days of treatment with 100 nM dexamethasone, GH secretion had increased to 190% and GH content to 230% of control. In contrast to the effects on GH, dexamethasone suppressed PRL secretion in a dose-dependent way, but this effect was seen only after 7 days of treatment and not after 4 days of treatment. Cycloheximide and actinomycin D prevented the stimulatory effect of dexamethasone on GH secretion. However, 24 h after cessation of cycloheximide treatment GH secretion was stimulated by dexamethasone. Four days of treatment with 100 nM dexamethasone did not affect the GH response to somatostatin, prostaglandin E1, and theophylline, nor the PRL response to dopamine, TRH, and theophylline. Thus, culture conditions may affect GH production, and dexamethasone can be used to culture somatotrophs for longer periods with steady GH production and normal responsiveness.
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PMID:Growth hormone secretion by cultured rat anterior pituitary cells. Effects of culture conditions and dexamethasone. 613 99

Specific binding sites for secretin have been identified in rat fundic membranes, using 125I-secretin. The binding was saturable, reversible, time and temperature dependent. Optimal pH for binding was around 7-7.5. Scatchard plots were compatible with the existence of 2 classes of receptors; the first class with a high affinity for secretin (apparent Kd of 4 x 10(-10) M) and a low binding capacity (150 fmol per mg membrane protein, i.e., 4,500 high affinity sites/cell) and a class of receptors with a lower affinity (Kd of 3 x 10(-9) M) and a higher binding capacity (580 fmol per mg membrane protein i.e., 17,400 sites/cell). Glucagon, gastric inhibitory polypeptide and somatostatin had no-effect on secretin binding. In contrast, VIP inhibited 125I-secretin binding and stimulated adenylate cyclase activity, in both cases at a 200-times lower potency than secretin (ID50 and Ka = 2 x 10(-7) M VIP). The properties of these secretin receptors strongly support the concept that secretin acts as a regulatory peptide on the rat gastric epithelium.
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PMID:Secretin binding sites coupled with adenylate cyclase in rat fundic membranes. 628 94


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