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)

Juvenile diabetic patients were studied 60-72 hours after insulin withdrawal when moderate ketoacidosis had developed. Somatostatin infusion for 4 hours in five patients resulted in almost complete suppression of plasma pancreatic glucagon and growth hormone, a fall in plasma-cyclic-adenosine-monophosphate (A.M.P.) concentrations, and a large fall in plasma-glucose concentration. After infusion plasma concentrations of these substances rose again. Blood-ketone-bodies, plasma-free-fatty-acids (F.F.A.), and plasma glycerol concentrations, however, did not decrease appreciably with somatostatin administration. In three patients 2 to 3 h somatostatin infusions were twice superimposed upon a continuous 9-5 h insulin infusion (1 unit/h). An insulin effect was noticeable within 30 minutes, with pronounced falls in the concentrations of plasma glucose, pancreatic glucagon, F.F.A., and blood-ketone-bodies. There was no significant change in these patterns when somatostatin was administered or withdrawn. These results do not indicate that somatostatin infusion would be useful in the treatment of manifest diabetic ketoacidosis.
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PMID:Failure of somatostatin to correct manifest diabetic ketoacidosis. 5 30

In order to understand the mechanism by which cyclic 3':5'-adenosine monophosphate (cAMP) regulates insulin secretion, cAMP-dependent protein phosphorylation was studied in a transplantable hamster islet cell tumor. Single cell suspensions prepared by enzymatic digestion of the tumors released insulin into the incubation media. Glucagon (3 nM to 3 muM) stimulated cellular cAMP accumulation and insulin release in a dose-dependent manner and these effects were enhanced by 1 mM theophylline. 8-Bromoadenosine 3':5'-monophosphate (8Br-cAMP) (1 mM) increased insulin release. Somatostatin (10 mug/ml) inhibited basal and glucagon or 8Br-cAMP-stimulated insulin release without significantly lowering cellular cAMP in glucagon-stimulated cells. For analysis of phosphoproteins, cells were incubated with carrier-free 32Pi following which lysates were prepared and analyzed by sodium dodecyl sulfate slab gel electrophoresis and autoradiography. Of the numerous 32P-labeled protein bands found, only one (P1, Mr = 28,000) displayed a significant increase in 32P incorporation when cells were incubated under conditions that raise the concentration of cellular cAMP. Somatostatin did not affect 32P incorporation into P1 or any other protein band. When cells were incubated with glucagon, an increase in cellular cAMP was evident after 1 min, enhanced 32P incorporation into P1 after 1 to 5 min, and stimulation of insulin release after 5 to 10 min. Analysis of subcellular fractions led to the designation of P1 as a 40 S ribosomal protein. Two-dimensional electrophoresis of 32P-labeled basic ribosomal proteins showed two labeled proteins, P1 and P2, both of which were localized to the 40 S ribosomal subunit. Only phosphorylation of P1 was stimulated by cAMP. The cAMP-dependent ribosomal phosphoprotein, P1, may be identical with a ribosomal phosphoprotein demonstrated in a variety of tissues and species. Its physiological role remains to be established.
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PMID:Cyclic adenosine 3':5'-monophosphate-mediated insulin secretion and ribosomal protein phosphorylation in a hamster islet cell tumor. 18 14

The effect of somatostatin on insulin release by incubated slices of rat pancreas was studied. Somatostatin inhibited insulin release induced by arginine/glucose (A/G), glucagon, glibenclamide, pentoxifyllin, 3',5'-adenosine monophosphate (cAMP), phentolamine, and KCl. When A/G was used as a stimulus, the quantial inhibitory effect of somatostatin was not neutralized by progressively increasing glucose concentrations. The alpha adrenergic blocking agent phentolamine, the phosphodiesterase inhibitors theophylline (10 mM) or pentoxifyllin (10 mM), and KCl partially reversed the inhibitory effect of somatostatin on A/G stimulation. The maximal reversal of somatostatin inhibition was obtained when the slices of pancreas were stimulated with A/G in the presence of the calcium ioniphore A23187 plus ATP. These results suggest that the inhibitory effect of somatostatin on insulin secretion could result from calcium translocation in pancreatic beta cells.
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PMID:Studies on the mode of action of somatostatin on insulin secretion. 19 19

In vitro, we were able to induce a differentiation of human (SK-N-MC, IMR-32, Leo-2) and murine neuroblastoma cells (NA-2, C-1300, NIE-115) with dibutyryl cyclic 3'5'-adenosine monophosphate (dbcAMP), hypothalamic factor (HF), and somatostatin. As morphological criteria of cellular differentiation we used the decrease in cell proliferation and the formation of neurites. Functional parameters were the increase of A cholinesterase activity, cAMP level, and protein content, and the decrease of cGMP level. After application of dbcAMP and HF, the effects were stronger than after somatostatin. We believe that the action of HF and somatostatin is caused by an increase in cAMP levels. In the in vivo experiments, human and murine neuroblastoma cells (NA-2, C-1300, and Leo-2) were transplanted into nude/nude mice. After HF treatment of 14 mice with NA-2 tumors, 4 of the mice were tumor-free, and mean tumor weight was reduced to one-third of the controls. Of the animals with C-1300 and Leo-2 tumors, half became tumor-free, and mean tumor weight was reduced to one-fourth. The results indicate that the induction of cellular differentiation by factors and hormones may in future become a method of therapy for human neuroblastoma.
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PMID:Research on the differentiation of human and murine neuroblastoma cells. 167 82

We have shown in the companion paper that somatotrophs dispersed from streptozotocin diabetic rats exhibit altered sensitivity to the natural hypothalamic controlling hormones, growth hormone releasing factor and somatostatin. We have further studied the effects on growth hormone release from dispersed adenohypophysial cells of normal and streptozotocin diabetic rats of stimulation by compounds that increase cyclic 3',5'-adenosine monophosphate formation or inhibit its breakdown and of a phorbol ester. The cells of the diabetic rats had no change in sensitivity in response to either cholera toxin or forskolin. A phosphodiesterase inhibitor caused an equal GH release from cells of both diabetic and normal animals after 60 min of incubation. There was no change in sensitivity of the cells of diabetic animals or in the maximal response of these cells to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate when compared with normal cells. A low calcium medium that blocked growth hormone releasing factor stimulated growth hormone release from normal rat cells also blocked it from the cells of the diabetic rats. These results suggest that the defect in response of the somatotrophs of diabetic animals is specific and only occurs with the hypothalamic hormones and not with other secretagogues.
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PMID:Altered release of growth hormone from dispersed adenohypophysial cells of streptozotocin diabetic rats. II. Effects of a phorbol ester and secretagogues which increase cyclic AMP. 248 23

The presence of vasoactive intestinal polypeptide (VIP) receptors coupled to an adenylate cyclase was demonstrated on membranes of neurons or glial cells grown in primary cultures originating from the cerebral cortex, striatum, and mesencephalon of mouse embryos. A biphasic pattern of activation was observed in all these cell types, involving distinct high- and low-apparent-affinity mechanisms. The absence of additive effects of VIP and 3,4-dihydroxyphenylethylamine (DA, dopamine), isoproterenol (ISO), and 5-hydroxytryptamine (5-HT, serotonin) suggests that the peptide receptors are colocated with each of the corresponding amine receptors on neuronal membranes of the three structures studied. The nonadditivity between the VIP- and ISO-induced responses on cortical and striatal glial membranes reveals as well a colocation of VIP and beta-adrenergic-sensitive adenylate cyclases on the same cells. A subpopulation of mesencephalic glia could possess only one of the two types of receptors, as a partial additivity of the VIP and ISO responses was seen. In addition, VIP modified the characteristics of the somatostatin inhibitory effect on adenylate cyclase activity of neuronal membranes from the cerebral cortex and striatum but not from those of the mesencephalon. On striatal and mesencephalic glial membranes the somatostatin inhibitory effect was observed only in the presence of VIP. However, as previously seen with ISO, the presence of VIP did not allow the appearance of a somatostatin inhibitory response on cortical glial membranes. This suggests that cortical glia are devoid of somatostatin receptors.
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PMID:Vasoactive intestinal polypeptide receptors linked to an adenylate cyclase, and their relationship with biogenic amine- and somatostatin-sensitive adenylate cyclases on central neuronal and glial cells in primary cultures. 285 67

The effect of chemical stimulation of the central nervous system was studied in anesthetized rats. (Bu)2 cAMP, cAMP, 5'-adenosine monophosphate (AMP), ATP, and (Bu)2 N6,O2-dibutyryl guanosine-3'5'-cyclic monophosphate sodium salt were injected directly into the third cerebral ventricle, and changes in hepatic venous plasma glucose, immunoreactive glucagon, and insulin concentrations were studied. The injection of (Bu)2cAMP (1 X 10(-8) to 5 X 10(-7) mol/microliter saline) into the third cerebral ventricle caused a dose-dependent hyperglycemia associated with increased immunoreactive glucagon. (Bu)2cAMP-induced hyperglycemia and hyperglucagonemia were inhibited by prior bilateral adrenalectomy. The injection of somatostatin (1 X 10(-9) mol) with (Bu)2cAMP (5 X 10(-7) mol) into the third cerebral ventricle abolished both (Bu)2cAMP-induced hyperglycemia and an increase of glucagon secretion. These results suggest that cAMP may act intracellularly within the central nervous system to increase hepatic glucose output, and this appears to depend on the adrenal gland. Epinephrine secreted from the adrenal gland may directly act on the liver or enhance glucagon secretion, which in turn increases hepatic glucose output.
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PMID:Increase in plasma glucose concentration after intracerebroventricular injection of N,O'-dibutyryl cyclic adenosine 3',5'-monophosphate. 287 22

Short-lasting hypothermia during thiobutabarbital general anaesthesia causes no decrease of the absolute ATP level in the blood and liver of rats. The adenylate energy charge in the tissues is relatively high - 0.86 in the liver and 0.85 in the muscles, which might be an evidence of a significant "energy sparing" during moderate hypothermia (26 +/- 1 degree C). Somatostatin in a dose of 20 micrograms/kg of body weight given to the rats during hypothermia decreased the ATP level, the ATP/ADP ratio and the adenylate energy charge in the studied tissues, especially in the liver, evidencing increased intensity of catabolic processes caused by the inhibitory action of somatostatin on the release of insulin and glucagon, among other hormones, and on the change of the insulin/glucagon ratio.
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PMID:Somatostatin effect on the level of adenyl nucleotides in the blood and tissues of rats during short-lasting hypothermia. 614 95

The novel 38-amino acid neuropeptide PACAP (pituitary adenylate activating peptide) has recently been shown to induce the pancreatic acinar tumour AR4-2J cell growth. This growth promoting effect of PACAP was, however, independent of adenylate cyclase activation but suppressed by pertussis toxin and the somatostatin analog SMS 201-995. This study was undertaken to search for potential cell signalling pathways involved in the growth promoting effect of PACAP on AR4-2J cells. The AR4-2J cells were grown in Dulbecco's Modified Eagle's Medium containing 10% foetal calf serum. For studies on cell signalling pathways, all experiments were carried out on cells which have reached 50 to 75% confluency. At that point, they were transferred to serum free medium overnight with or without 1 microCi/ml myristic acid. The next morning, cells were harvested, washed and used for tyrosine kinase and phospholipase D (PLD) activities. For studies on growth, cells were grown for 2 days in the presence of 1 nM PACAP +/- the different inhibitors of tyrosine kinase and PLD. PACAP-38 and -27 caused a dose-dependent and parallel activation of tyrosine kinase and PLD an effect prevented by the antagonist PACAP 7-38. PACAP-38-stimulated tyrosine kinase and PLD activation are both dose-dependently inhibited by SMS 201-995. Finally, PACAP-stimulated tyrosine kinase and PLD activities are both inhibited by cell's preincubation with genistein and pertussis toxin. After 2 days, the PACAP-induced increase in AR4-2J cell growth was significantly inhibited by increasing concentrations of genistein and wortmannin, inhibitors of tyrosine kinase, PLD and phosphatidylinositol 3-kinase, respectively. PACAP can induce concomitant activation of tyrosine kinase and PLD; this finding and the observation that inhibition of these two enzymes inhibited PACAP-induced AR4-2J cell growth strongly suggests that they are intimately involved in the overall process of PACAP-induced AR4-2J cell proliferation.
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PMID:Cell signalling pathway involved in PACAP-induced AR4-2J cell proliferation. 766 8

Somatostatin and cortistatin have been shown to act directly on pituitary somatotrophs to inhibit growth hormone (GH) release. However, previous results from nonprimate species indicate that these peptides can also directly stimulate GH secretion, at low concentrations. The relevance of this phenomenon in a nonhuman primate model was investigated in the present study by testing the impact of somatostatin/cortistatin on GH release in primary pituitary cell cultures from baboons. High doses (> 10(-10) m) of somatostatin/cortistatin did not alter basal GH secretion but blocked GH-releasing hormone (GHRH)- and ghrelin-induced GH release. However, at low concentrations (10(-17)-10(-13) m), somatostatin/cortistatin dramatically stimulated GH release to levels comparable to those evoked by GHRH or ghrelin. Use of somatostatin receptor (sst) specific agonists/antagonists, and signal transduction blockers indicated that sst2 and sst1 activation via intact adenylate cylcase and mitogen-activated protein kinase systems mediated the inhibitory actions of high-concentration somatostatin. By contrast, the stimulatory actions of low-dose somatostatin on GH release were mediated by sst5 signalling through adenylate cylcase/cAMP/protein kinase A and intracellular Ca(2+) pathways, and were additive with ghrelin (not GHRH). Notably, low-concentrations of somatostatin, similar to sst5-agonists, inhibited prolactin release. These results clearly demonstrate that the ultimate impact of somatostatin/cortistatin on hormone release is dose-dependent, cell type-selective and receptor-specific, where the stimulatory effects of low-concentration somatostatin/cortistatin on GH release extend to primates, thereby supporting the notion that this action is relevant in regulating GH secretion in humans.
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PMID:Somatostatin dramatically stimulates growth hormone release from primate somatotrophs acting at low doses via somatostatin receptor 5 and cyclic AMP. 2212 35


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