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)

This study was aimed at evaluating the effect of theophylline, a drug that increases the intracellular concentrations of cAMP by inhibiting phosphodiesterase activity, on somatostatin (SRIF)-mediated inhibition of insulin secretion in man. Acute insulin response (AIR) to i.v. glucose (mean change 3-10 min) was almost totally suppressed by SRIF (500 micrograms/h) and glucose utilization was reduced (p less than 0.0001). These SRIF-induced decreases failed to be eliminated by a concurrent infusion of theophylline (100 mg as a loading dose followed by a constant infusion of 5 mg/min). Theophylline alone resulted in a significant increase in both AIR (p less than 0.01) and glucose removal rates (p less than 0.05). Thus, our data disprove the involvement of the phosphodiesterase enzymes in the inhibitory action of SRIF on glucose-induced insulin secretion in man.
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PMID:Somatostatin and insulin secretion in man. II. The effect of theophylline. 4 65

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

Since growth hormone (GH) and prolactin (Prl) secretion by human pituitary tumours is often influenced by the hypophysiotrophic hormones thyrotrophin-releasing hormone (TRH) and somatostatin (SRIF), we have examined the responses of several transplantable rat pituitary tumours to these substances in a perifusion apparatus. The MStT/W15 tumour did not alter its secretion of GH and Prl in response to TRH, SRIF, or a partially purified porcine hypothalamic extract containing GH-releasing activity; normal rat pituitaries show clear responses to each of these substances. Theophylline and dibutyryl cyclic AMP each provoked increased GH and Prl release from the tumour. A second specimen of the MStT/W15 tumour and a specimen of the MStT/W5 tumour behaved in a manner identical to the original MStT/W15, showing no response to TRH or SRIF, but releasing both GH and Prl when theophylline or dibutyryl cyclic AMP was given. The MtT/F4 tumour increased its secretion of GH in response to TRH, 10 mug/ml, and theophylline, but no effect was seen with lower concentrations of TRH or with SRIF; Prl secretion by the F4 tumour was increased by theophylline, but TRH and SRIF had no effect. The autonomy demonstrated in these experimental tumours may be due to a loss of specific hypophysiotrophic hormone receptors or of secretory activating mechanisms.
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PMID:Altered responsiveness to hypophysiotrophic hormones of perifused rat pituitary tumours. 19 Aug 40

Certain aspects of radio-immunoassay of somatostatin from isolated rat pancreatic islets are described. Somatostatin-14, and not somatostatin-28, is secreted from isolated rat pancreatic islets. Less somatostatin secretion is measured per islet owing to purity of tracer in the radio-immunoassay. Theophylline apparently cross-reacts with somatostatin in the assay described, and this has to be taken into consideration when studying somatostatin release induced by theophylline in isolated islets.
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PMID:Radio-immunoassay of somatostatin from isolated rat pancreatic islets. 257 83

In an attempt to delineate the mechanism(s) of PRL secretion from human lactotrophs, the effects of dopamine and somatostatin on PRL release from adenomatous and nonadenomatous human pituitary cells in culture was studied. High K+ and the divalent cation ionophore A23187 both elevated PRL secretion, which was blocked by dopamine and somatostatin. When the cells were incubated in low calcium medium, PRL secretion was significantly inhibited. The addition of dopamine or somatostatin to low calcium medium further decreased PRL release. The stimulatory action of ionophore A23187 on PRL release was found even in the absence of extracellular calcium. Theophylline and isobutylmethylxanthine, when added to the incubation medium, increased PRL secretion, and dopamine as well as somatostatin again inhibited PRL release induced by phosphodiesterase inhibitors. No qualitative difference in these PRL responses was found in adenomatous and nonadenomatous human lactotrophs. In prolactinoma cells obtained from three different patients, cAMP generation was correlated with hormone release. Exposure of the cells to dopamine or somatostatin resulted in a parallel decrease in intracellular cAMP content and PRL secretion. The inhibitory effect of dopamine on PRL secretion and cAMP accumulation was blocked by coincubation of the cells with haloperidol. These results suggest that an increase in cytosol calcium caused by either mobilization from intracellular calcium pools or influx from the extracellular compartment and intracellular cAMP accumulation may be involved in the mechanism of PRL secretion from human lactotrophs, and dopamine and somatostatin may influence these two messengers to suppress PRL secretion.
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PMID:Mechanism of the inhibitory action of dopamine and somatostatin on prolactin secretion from human lactotrophs in culture. 257 87

Regulation of insulin release and transmembrane Ca2+ fluxes was examined using pieces of 3 benign medullary-type insulinomas removed from the pancreas of female patients at surgery. Immunocytochemical staining confirmed the presence of insulin-containing cells with no demonstrable glucagon, somatostatin or pancreatic polypeptide. After 3 days of culture in RPMI-1640, tumour pieces released 11-158 mg insulin kg-1 dry wt during acute 60 min incubations with the concomitant uptake of 2-47 mmol 45Ca kg-1 into the intracellular lanthanum-nondisplaceable pool. At 2.56 mM Ca2+, glucose alone or in combination with glyceraldehyde, mannoheptulose or diazoxide did not modify insulin release or 45Ca uptake. Theophylline significantly increased insulin release from 2 tumours with a small stimulatory effect on the third. A depolarising concentration of K+ enhanced insulin release from one tumour but this was not associated with an increase of 45Ca uptake. Calcium antagonists, (verapamil, D-600 and trifluoroperazine) and calcium ionophores (A23187 and Br-X537A) failed to modify insulin release or 45Ca uptake by each of the two tumours tested. Evaluation of 45Ca efflux from one tumour confirmed the unresponsiveness to glucose, K+, verapamil and A23187. Prolonged culture of 2 tumours for up to 16 days was associated with the gradual decline of insulin release to a steady output of 2-15 ng 24 h-1. Addition of verapamil to the cultures inhibited insulin output from one tumour, but mannoheptulose or diazoxide were without effect. The results indicate that inappropriate insulin release from these 3 benign medullary-type insulinomas is associated with disturbances in the regulation of transmembrane Ca2+ fluxes.
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PMID:Defective regulation of insulin release and transmembrane Ca2+ fluxes by human islet cell tumours. 282 49

Platelet-activating factor (PAF) has recently been shown to be a potent ulcerogenic agent in the stomach and intestinal mucosa. Its extract mechanism of action is not yet known although histological studies suggest that vasocongestion is an important feature of PAF-induced damage. We have therefore studied the activity of various agents with different modes of action toward PAF-induced gastrointestinal lesions in the rat (PAF 2 micrograms/kg i.v.; macroscopic lesions of tissue scored 20 min later; arbitrary scale from 0 to 4). Drugs were administered either i.m., s.c. (5 min) or orally (30 min) before PAF injection. PAF-induced gastric lesions were strongly inhibited by the natural PAF-antagonist BN 52021 as well as by atropine sulphate and cimetidine which implicates cholinergic stimulation in the ulcerogenic activity of PAF. The somatostatin analog BIM 23014 was also very potent against PAF, perhaps by reducing the parasympathetic stimulation in the gastric wall as described for somatostatin. Allopurinol, which is a free radical scavenger also almost totally inhibited PAF-induced gastric damage, suggesting that neutrophils are involved in the mucosal lesions. The considerable inhibition of the gastric effects of PAF found in neutrophil-depleted animal supports this hypothesis. Theophylline and disodium cromoglycate, mast cell stabilizing drugs which were also active in our model, could act by protecting mast cell degranulation induced by free radicals released from activated neutrophils. A multifunctional process seems to determine the mucosal gastric damage induced by PAF, but parasympathetic stimulation and neutrophil activation play a major role in this pathology.
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PMID:Role of neutrophils in gastric damage induced by platelet activating factor. 324 84

We studied the effects of acute, intraperitoneal administration of caffeine on serum thyrotropin (TSH), growth hormone, prolactin, thyroxine and 3,3',5-triiodothyronine in rats. Caffeine lowered serum TSH and GH in a dose-dependent manner with ED50 values of 30 and approximately 50 mg/kg, respectively. TSH levels were depressed 1 to 6 hr after injection and correlated with serum caffeine levels greater than 20 micrograms/ml. The decrease in serum TSH was followed by decreases in serum 3,3',5-triiodothyroxine and thyroxine 4 hr after caffeine administration. Theophylline and theobromine had effects similar to those of caffeine on hormone levels. Caffeine did not significantly affect hormone secretion when incubated directly with rat pituitaries in vitro. Administration of antisomatostatin antiserum to rats blocked the inhibitory effects of caffeine on serum GH levels, suggesting that caffeine inhibits GH and TSH secretion by releasing hypothalamic somatostatin.
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PMID:Effects of caffeine on anterior pituitary and thyroid function in the rat. 610 18

An in-vitro study of GH secretion by rat fetal and neonatal pituitary glands was conducted using a perifusion system. After a 2 h period the GH content of the effluent was constant. Theophylline, thyrotrophin releasing hormone (TRH) and rat stalk median emience extract (SME) were effective stimuli of GH release from the pituitary glands of the 19.5-day-old fetuses. Somatostatin, added to the medium (10 microgram/ml), had no inhibitory effect on GH release (basal or stimulated by either theophylline or SME) before day 4 after birth. After postnatal day 5, somatostatin always inhibited GH secretion. These findings were consistent with the results of experiments in vivo. In rats tested within 4 days of birth, sodium pentobarbitone-stimulated plasma GH levels were not reduced by somatostatin; on day 4 and thereafter somatostatin depressed the response to pentobarbitone injection. These results indicate a postnatal maturation of the regulation of GH release by the hypothalamo-hypophysial system in the rat.
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PMID:Ontogenetic development of the inhibition of growth hormone release by somatostatin in the rat: in-vivo and in-vitro (perifusion) study. 611 24

Growth hormone (GH) and prolactin (Prl) secretion by a normal human pituitary in dispersed cell culture has been investigated. Prl secretion was significantly stimulated after 0.5, 1, 2 and 4 h exposure to 1, 10, 100 and 1000 ng/ml thyrotrophin releasing hormone (TRH). Maximal effects were obtained with 10 ng/ml TRH at 2 h, higher doses being less effective. GH secretion was unchanged with the exception that 1 ng/ml TRH produced a small decrease at 4 h. GH and Prl secretion was significantly inhibited by incubation with 0.01, 0.1, 1 or 10 micrograms/ml 2-bromo-alpha-ergocryptine (bromocriptine). The inhibition persisted for a further 24 h after removal of bromocriptine. Theophylline (10(-2) M) significantly increased GH and Prl secretion during a 4 h incubation and this effect was blocked by co-incubation with 10 ng/ml somatostatin (SRIF). SRIF also inhibited basal GH and Prl secretion during 4 h and removal of SRIF and incubation for at further 4 h led to a rebound in GH and Prl secretion to levels greater than control. It is concluded that cell culture techniques previously applied to the study of hormone secretion by pituitary adenomas can be equally applied to the normal human pituitary.
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PMID:Growth hormone and prolactin secretion by dispersed cell cultures of a normal human pituitary: effects of thyrotrophin releasing hormone, theophylline, somatostatin, and 2-bromo-alpha-ergocryptine. 611 69


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