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)

1. Dibutyryl cyclic AMP (Db cAMP, 75-500 microgram/kg), injected into the lateral ventricle of the brain of the cat increased blood pressure, heart rate and splanchnic discharge rate. 2. ATP, but not AMP, induced similar changes; GMP in small doses increased blood pressure. 3. A number of drugs are known to activate adenylate cyclase-induced hypertension, tachycardia and increase splanchnic discharge rate. This was shown for TRH, tetracosactide and a new beta2-adrenoceptor stimulant, NAB 365. 4. Injection into the lateral ventricle of theophylline or Ro 7/2956, both inhibitors of phosphodiesterase, similarly increased blood pressure. 5. Histamine administered by the same route induced similar reactions; it is not known if this action was exerted by activation of H1- or H2-receptors. 6. Somatostatin, known to reduce cAMP levels, induced a small but significant decrease in blood pressure. Melanocyte stimulating hormone release inhibiting factor (MIF) and TSH were ineffective. 7. These results provide evidence for the possibility of a role for cAMP in the central regulation of blood pressure at suprabulbar levels.
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PMID:Cyclic 3'5'-adenosine monophosphate and central circulatory control in cats and dogs. 2 Feb 56

An insulin-producing islet cell tumor of the Syrian hamster has been studied in vitro for its capacity to respond to known stimuli of insulin release. Insulin secretion during short term incubation and perifusion of fragments of tumor was detected by radioimmunoassay. Insulin release was increased 2-4 fold by 40 mM potassium in the presence of calcium, glucose (22 mM), glucagon (0.3-3.0 muM), N6,02'-dibutyryl adenosine 3',5'-monophosphate (cAMP; 6mM), and theophylline (10 mM). Concentrations of glucagon that induced insulin release were also effective in activating adenylate cyclase in the membranes of tumor cells. Thus, this tumor appears to possess a cAMP-mediated mechanism for insulin release. Somatostatin (0.8-25 mum) inhibited glucagon-induced insulin release without altering basal or glucagon stimulated adenylate cyclase activity. It would appear that inhibition of glucagon induced insulin release by somatostatin is not mediated by adenylate cyclase. We propose that insulin release by this tumor is sufficiently similar to that found in normal islets so as to make it a suitable model for biochemical studies that require large quantities of homogeneous tissue.
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PMID:Regulation of in vitro insulin release from a transplantable Syrian hamster insulinoma. 16 25

Studies of TSH release and production were performed in short term monolayer cultures of transplantable, thyroid hormone responsive, thyrotropin (TSH) producing mouse pituitary tumors. These tumors contained large amounts of TSH, small amounts of growth hormone (GH) and no detectable luteinizing hormone (LH), indicating that the predominant hormone product of tumor cells was TSH. The TSH content per tumor cell was similar to that of the normal pituitary where thyrotrophs represent a small fraction of the total cells, suggesting that the TSH content per tumor cell was less than that of the normal thyrotroph. There was a time dependent release and production of TSH by tumor cells in monolayer culture. Thyrotropin releasing hormone (TRH) increased the release into the media and the production of TSH in a dose dependent manner. Maximum effects were noted at 0.2 ng/ml. Thyroid hormones and somatostatin inhibited both basal and TRH induced effects on both TSH release and production. TSH release as induced by TRH was calcium dependent. TSH release was stimulated by ouabain (10(-3)M) and potassium (57 mM), agents known to promote cellular calcium uptake in a calcium dependent manner. These studies indicate that tumor derived cells function in monolayer culture in a similar fashion to normal thyrotrophs. Studies were conducted to test the hypothesis that TRH action is mediated by adenosine 3',5' monophosphate (cAMP). Dibutyryl cAMP (6 mM) and theophylline (10 mM) increased TSH release suggesting that cAMP is involved in TSH release. However, TRH had no detectable effect on tumor cell adenylate cyclase activity or levels of cAMP. In contrast, PGE1 (1-10 mug/ml) stimulated adenylate cyclase activity and elevated cellular levels of cAMP without increasing TSH release. Thus, we are unable to confirm the postulate that cAMP is the intracellular mediator of TRH action.
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PMID:Regulation of thyrotropin (TSH) release and production in monolayer cultures of transplantable TSH-producing mouse tumors. 17 85

Four-day-old pituitary monolayer cultures were incubated with various hypothalamic releasing hormones. Rat hypothalamic extract stimulated the release of LH, FSH, and PRL by these cultures in a dose-related fashion. Synthetic LH-RH stimulated the release of LH and FSH but not of PRL. Synthetic TRH increased the release of PRL but had no effect on LH or FSH. At 10(-8) M, somatostatin did not affect any of the three adenohypophyseal hormones. Incubation with DBcAMP or theophylline also stimulated PRL release without any detectable effect on LH and FSH release. These data suggest the involvement of cyclic AMP--adenylate cyclase system in the mechanism of PRL release, but their involvement in gonadotropin release requires further studies.
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PMID:Effects of hypothalamic-releasing hormones on LH, FSH, and prolactin in pituitary monolayer cultures. 17 71

The effects of somatostatin on insulin release and cyclic AMP metabolism were studied in collagenase-isolated islets of Langerhans from the rat. Ceoncentrations from 500 to 2000 ng/ml significantly inhibited glucose stimulated insulin release, while 100 and 200 ng/ml were ineffective. Somatostatin (2000 ng/ml) inhibited insulin release and [3H]-cyclic AMP accumulation induced by 16.7 mM glucose after 10 and 30 min of incubation. In dose-response studies, the inhibition by somatostatin of the effect of glucose on [3H]cyclic AMP and insulin release could be overcome by a high concentration of the hexose (44.9 mM), suggesting competitive inhibition. In the absence of glucose, somatostatin inhibited [3H]cyclic AMP accumulation induced by the phosphodiesterase inhibitor, IBMX, while no inhibition was seen, again in the absence of hexose, when the [3H]cyclic AMP levels had been raised by the adenyl cyclase stimulator, cholera toxin. Somatostatin did not affect phosphodiesterase activity when added to islet homogenates, but preincubation of the islets with the peptide before homogenization decreased the activity by about 30%. It is suggested that somatostatin-induced inhibition of insulin release is, at least partially, mediated by cyclic AMP, probably through an action on islet adenyl cyclase.
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PMID:Studies on the mechanisms of somatostatin action on insulin release. IV. effect of somatostatin on cyclic AMP levels and phosphodiesterase activity in isolated rat pancreatic islets. 19 42

Fluoride-stimulated adenylate cyclase is demonstrated inisolated tumor cells of transplantable rat pituitary tumor MtT-F4 in vitro. The intracellular cyclic adenosine 3':5'-monophosphate is lowered in the cells incubated in the presence of synthetic somatostatin. Contrary to the findings reported for normal pituitary, however, the immunoreactive growth hormone release does not change when either somatostatin or phosphodiesterase inhibitors are present in the incubation medium. The presence of dibutyryl cyclic adenosine 3':5'-monophosphate (5 mM) in the incubation medium does not change the rate of growth hormone release by isolated tumor cells.
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PMID:Effect of somatostatin on growth hormone release by MtT-F4 rat pituitary tumor in vitro. 19 84

Short term (30 min) infusion of cyclic somatostatin (50 microgram/rat), insulin (1 U/rat) or the two together significantly suppressed urinary cyclic AMP excretion in streptozotocin-diabetic rats. While somatostatin tended to increase cyclic GMP excretion, insulin had an opposite effect in diabetic but not in normal rats. It is suggested that somatostatin suppresses cyclic AMP excretion by inhibiting directly adenylate cyclase in liver and perhaps in other organs. The possibility that suppression of urinary cyclic AMP is due to inhibition of glucagon secretion is also considered.
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PMID:Somatostatin inhibits urinary cyclic AMP excretion in diabetic rats. 19 95

Glucose-induced insulin secretion is enhanced by a preceeding glucose stimulus. The characteristics of this action of glucose were investigated in perfused pancreas and collagenase-isolated islets of Langerhans. A 20- to 30-min pulse of 27.7 mM glucose enhanced both the first and second phase of insulin release in response to a second glucose stimulus by 76-201%. This enhancement was apparent as an augmented maximal insulin release response to glucose. The effect of priming with glucose was seen irrespective of whether the pancreatic tissue was obtained from fed or fasted rats. Separating the two pulses of hexose by a 60-min time interval of exposure to 3.3 mM glucose did not abolish the potentiation of the second pulse. Omission of Ca(++) as well as the inclusion of somatostatin or mannoheptulose during the first pulse abolished insulin secretion during this time period; however, only the inclusion of mannoheptulose deleted the potentiation of the second pulse. d-Glyceraldehyde, but not pyruvate, d-galactose, or 3-isobutyl-1-methylxanthine, could substitute for glucose in inducing potentiation. In islets labeled with [2-(3)H]adenine, the [(3)H]cyclic AMP response to glucose was increased by 35% when measured after 1 min, but was increased only marginally after 2-10 min of stimulation with a second pulse of glucose. The production of (3)H(2)O from glucose was not affected by glucose priming. It is concluded that (a) the induction of the glucose-induced, time-dependent potentiation described here is dependent on glucose metabolism but not on stimulation of cyclic AMP, calcium fluxes, or insulin release per se; (b) the mechanisms that mediate the pancreatic "memory" for glucose are unknown but do not seem to involve to a major extent an increased activity of the adenylate cyclase-cyclic AMP system of the beta-cell; (c) the evidence presented supports the hypothesis of a dual role of glucose for insulin release.
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PMID:Immediate and time-dependent effects of glucose on insulin release from rat pancreatic tissue. Evidence for different mechanisms of action. 20 21

The effect of somatostatin on glucose-induced insulin secretion and cyclic AMP accumulation in isolated islets from obese, hyperglycemic ob/ob mice was studied in a microperifusion system. The normal biphasic pattern of insulin release as well as the inhibitory pattern of insulin release produced by somatostatin (0.5--1 microgram/ml) was matched by similar changes in the intracellular concentration of cyclic AMP. When islets were stimulated by glucose (3 mg/ml) plus 3-isobutyl-1-methylxanthine (0.1 mM), somatostatin (0.5 microgram/ml) failed to inhibit insulin secretion or cyclic AMP formation in the second phase whereas in the first phase both parameters were significantly reduced by somatostatin (0.5 microgram/ml). In batch-type incubations it was shown that addition of excess calcium (to 6 mM) reversed this inhibition. In the second phase calcium potentiated the (glucose + 3-isobutyl-1-methylxanthine)-stimulated insulin secretion without affecting the cyclic AMP production. This potentiation was inhibited by somatostatin (0.1 microgram/ml). Somatostatin (1 microgram/ml) inhibited adenylate cyclase activity in islet homogenates. No effect of somatostatin on islet glucose utilization could be demonstrated. The results indicate a dual action of somatostatin in the inhibition of insulin release, one involving the islet adenylate cyclase and one affecting the islet uptake of calcium.
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PMID:The effect of calcium on somatostatin inhibition of insulin release and cyclic AMP production in mouse pancreatic islets. 22 49

1. Investigation of the ionic requirements of the in vitro insulin release system, which consists of cod islet plasma membrane and rabbit islet granules incubated at pH 6.5, showed that the presence of Ca(2+) was obligatory for the system to operate.2. Glucose-initiated insulin release was as effective in the presence of beta-gamma-methylene ATP, as it was in the presence of ATP. This analogue of ATP is a substrate neither for adenylate cyclase nor for any known animal membrane proteases. The effect of ATP on glucose mediated release is allosteric.3. Glucose (16 mM)-initiated insulin release was slower than that induced by glucose-6-phosphate (4 mM); 150 and 120 sec, respectively.4. The lag found with glucose-mediated insulin release was dependent upon glucose concentration. The lower the glucose concentration, the longer the lag. With 1 mM glucose the lag extended to 30 min.5. Once insulin release was initiated, the rate and amount of insulin release was independent of the glucose concentration.6. Pre-incubation of membranes with Ca(2+), glucose and ATP prior to the addition of granules, abolished the extended lag that had been obtained with 1 mM glucose. Events in the plasma membrane are the major contributor to the generation of the extended lag.7. The glucose analogue 5'thio-D-glucose, although not able to release insulin, was shown to compete with glucose for the glucoreceptor. By increasing the ratio of analogue to glucose the lag time increased. Thus, the lag time is dependent upon the ;effective' external glucose concentration.8. The max. amount of insulin released by 4 ng of membrane in the presence of glucose (16 mM) was 300 ng. The fact that membranes became refractory to glucose after this max. amount of insulin was released showed that recycling of release sites was not taking place in vitro and that granule: granule interactions were not occurring.9. The 120 sec lag before glucose-6-phosphate-initiated release was independent of glucose-6-phosphate concentration. The rate of insulin release with glucose-6-phosphate was concentration dependent.10. Glucose-6-phosphate did not cause further insulin release from a membrane that had released the max. amount of insulin it was capable of in the presence of glucose. The addition of tolbutamide (10 mM) to such a membrane did cause insulin release. This suggests that glucose and glucose-6-phosphate share a final common pathway.11. Adrenaline and somatostatin did not inhibit glucose-mediated insulin release.
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PMID:An in vitro system for studying insulin release: effects of glucose and glucose-6-phosphate. 33 48


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