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 effect of variations of intra-antral pH on the intraluminal release of somatostatin was studied. Acute pouches were created in anaesthetized cats, and the pouches were perfused with solutions differing in pH. Somatostatin levels were then measured in the perfusates. In this model phosphate buffer was a potent stimulator of intra-antral somatostatin release, whereas perfusion with 0.1 M HCl failed to release somatostatin by itself. Since phosphate buffer also releases gastrin, the releasing effect ought to be exerted beyond the mechanism that can be blocked by somatostatin. (Thus the stimulatory effect of phosphate buffer might be exerted on the membranes of the endocrine cells.)
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PMID:Phosphate buffer stimulates somatostatin release into the antral lumen of anaesthetized cats. 4 3

Antral somatostatin- and gastrin-producing cells (D and G cells) were studied in a group of patients with chronic renal failure (CRF) in comparison with a control group. Gastric acid secretion and serum gastrin, phosphate, and parathormone (PTH) levels were also evaluated in every patient. The group with CRF showed a mild increase both in G- and in D-cell denisty. In this group serum phosphate and PTH levels were higher than normal, showing hyperparathyroidism in every patient. A direct correlation was found between G-cell density and parathyroid function in patients with CRF. Hyperparathyroidism, therefore, seems to play a role in the mechanism of increased serum gastrin levels in CRF.
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PMID:Antral G- and D-cell counts in chronic renal failure. 37 75

We have recently shown that in rat parietal cells the glucagon-like peptide 1 (GLP-1) variants 7-36 amide, 1-37, and 1-36 amide stimulate H+ production as indirectly measured by [14C]aminopyrine (AP) accumulation. This response to the GLP-1 peptides was intracellularly mediated by activation of adenylate cyclase and by adenosine 3',5'-cyclic monophosphate (cAMP) as second messenger. In the present study, we compared prostaglandin (PG)E2, somatostatin, and the protein kinase A antagonist Rp-adenosine-3',5'-monophosphorothioate (Rp-cAMPS) with respect to their inhibitory effects on parietal cell function induced by GLP-1 or histamine. PGE2 and somatostatin noncompetitively inhibited AP accumulation and cAMP production in response to the GLP-1 variants and histamine (IC50): [mean inhibitory concn 5 x 10(-9) M PGE2; 3 x 10(-7) somatostatin]; at their maximal concentrations PGE2 (10(-7) M) and somatostatin (10(-6) M) caused 85 and 65% inhibition, respectively. Treatment with pertussis toxin (PT; 250 ng/ml; 4 h) reversed the inhibitory effect of PGE2 and somatostatin on AP accumulation and cAMP production. At 2 x 10(-3) M (IC50: 3 x 10(-4) M) Rp-cAMPS completely inhibited AP accumulation induced by the GLP-1 variants or histamine; this effect was insensitive to PT. Specificity of Rp-cAMPs as protein kinase A inhibitor is suggested by inhibition of AP accumulation in response to Sp-cAMPS and N6,O2-dibutyryl adenosine 3',5'-cyclic phosphate sodium, and forskolin, activators of protein kinase A and adenylate cyclase, respectively. We conclude that the parietal cell responses to GLP-1 and histamine are inhibited by identical mechanisms. Effects of PGE2 and somatostatin are mediated by the PT-sensitive subunit of adenylate cyclase Gi, whereas Rp-cAMPS interferes with cAMP-dependent mechanisms that are insensitive to PT.
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PMID:Pertussis toxin-sensitive and pertussis toxin-insensitive inhibition of parietal cell response to GLP-1 and histamine. 134 5

The effects of somatostatin-14 and bombesin on [3H]inositol phosphate accumulation were studied in 24 h myo-[3H]inositol-prelabeled cultured rat acinar cells. Bombesin, 10 nM, stimulated basal formation of phosphatidyl monophosphate (InsP1), phosphatidyl 4,5-biphosphate (InsP2) and inositol 1,4,5-triphosphate (InsP3) by 128 +/- 5.2%, 147 +/- 10% and 155 +/- 5%, respectively. At 5 s, the ED50 value for InsP3 stimulation was 0.70 +/- 0.2 nM. This stimulation was partly blocked (64 +/- 0.04% inhibition) by 10 ng/ml Bordetella pertussis toxin. In contrast to bombesin, somatostatin, 10 nM, inhibited basal InsP1, InsP2 and InsP3 formation. At 5 s, the inhibition degree for InsP3 was 18 +/- 2.5% and the IC50s values 1 +/- 0.09 nM, 1 +/- 0.12 nM and 0.07 +/- 0.005 nM for InsP1, InsP2 and InsP3, respectively. Bombesin-stimulated InsP3 formation was also inhibited by somatostatin. At 5 s, the inhibition degree was 85 +/- 3.5% at 10 nM and the IC50 value, 0.10 +/- 0.05 nM. Furthermore, somatostatin inhibition of bombesin stimulation was partly blocked (66 +/- 4% inhibition) by Bordetella pertussis toxin. These data therefore suggest that the acinar pancreatic cells contain a somatostatin receptor exerting a negative control on basal and bombesin receptor-stimulated phosphatidyl inositol turnover.
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PMID:Somatostatin inhibition of phosphoinositides turnover in isolated rat acinar pancreatic cells: interaction with bombesin. 135 13

Vasopressin (VP) stimulates insulin secretion and inositol phosphate (InsP) production in clonal hamster beta cells (HIT) via a cyclic AMP-independent V1-receptor-mediated signal-transduction pathway. Somatostatin (SRIF) inhibited VP-stimulated insulin secretion, and the effects of SRIF were abolished by pretreatment with pertussis toxin. The Ca(2+)-channel blockers verapamil and nifedipine also inhibited VP-stimulated insulin secretion during 20 min incubations, but verapamil was ineffective at 2 min, and the effects of SRIF and nifedipine together were not addictive. SRIF failed to inhibit further the attenuated insulin response to VP in Ca(2+)-free medium. VP-stimulated InsP production was also inhibited by SRIF in a pertussis-toxin-sensitive manner. Whereas VP-stimulated insulin secretion was almost completely inhibited by SRIF at an equimolar concentration, VP-stimulated InsP production was much less sensitive to inhibition by SRIF, even at a 100-fold excess concentration. VP increased cytosolic Ca2+ in HIT cells loaded with fura 2, the fluorescent Ca2+ indicator. The increase was biphasic, with an initial rapid spike increase followed by a prolonged second phase. Both SRIF, at a concentration which inhibited VP-stimulated insulin secretion but not InsP production, and verapamil failed to inhibit the rapid spike increase in intracellular Ca2+, but did inhibit the second phase. We conclude that VP induces biphasic changes in cytosolic Ca2+, secondary to mobilization of intracellular Ca2+ and influx of extracellular Ca2+. SRIF inhibits insulin secretion by interrupting influx of extracellular Ca2+, likely by inhibiting Gi-subunit activity. Inhibition of VP-stimulated phosphoinositide hydrolysis, which is also pertussis-toxin-sensitive, may represent an additional mechanism of action of SRIF.
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PMID:Somatostatin inhibits vasopressin-stimulated phosphoinositide hydrolysis and influx of extracellular calcium in clonal hamster beta (HIT) cells. 136 25

The effects of somatostatin and alpha 1-adrenergic receptor agonists on cytosolic Ca2+ in striatal astrocytes from the embryonic mouse in primary culture have been investigated by microfluorimetry. Methoxamine or somatostatin induced a transitory increase in cytosolic Ca2+, but their combined addition led to a sustained increase in cytosolic Ca2+ which seems to be due to a Ca2+ influx since it was not observed in the absence of external Ca2+. Voltage-independent Ca2+ channels contribute to this process. Indeed, voltage-operated calcium channels are not involved since neither dihydropyridines nor La3+ were effective in suppressing the sustained cytosolic Ca2+ elevation. Moreover, depolarization by 50 mM KCl, which was ineffective alone, suppressed the effect of somatostatin observed in the presence of the alpha 1 agonist, methoxamine. The implication of arachidonic acid in the observed potentiation is suggested by the following observations: 1) arachidonic acid induced a sustained elevation of cytosolic Ca2+ similar to that evoked by the co-application of methoxamine and somatostatin; 2) the addition of ETYA, an inactive and non-metabolizable analogue of arachidonic acid suppressed the calcium plateau produced by the agonists. In addition, direct activation of PKC by an exogeneous diacylglycerol analogue allowed somatostatin alone to evoke a sustained elevation of cytosolic Ca2+. Therefore, methoxamine through the successive activation of PLC and PKC could allow a lipase, probably PLA2, to be stimulated by somatostatin. Since arachidonic acid has already been shown to trigger the opening of K+ channels and the formation of inositol phosphates, somatostatin, through the arachidonic acid-mediated hyperpolarization could increase the Ca2+ driving force and thus improve Ca2+ influx through the inositol phosphate gated channels.
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PMID:Synergistic regulation of cytosolic Ca2+ concentration by somatostatin and alpha 1-adrenergic agonists in mouse astrocytes. 136 95

Acromegaly is characterized by growth hormone (GH) hypersecretion and insulin-like growth factor-I (IGF-I) excess, both of which stimulate osteoblast proliferation. At diagnosis, GH excess has usually been present for years. Furthermore, impaired gonadotropin secretion with hypogonadism is frequent. To date, studies of changes in bone mineral density (BMD) in acromegaly have been limited and the available data inconsistent. To investigate the effects of GH excess on proximal femur and lumbar spine BMD, a case series of 25 patients with acromegaly (8 eugonadal, 17 hypogonadal) documented by high plasma GH and IGF-I concentrations was studied. BMD was measured using dual-photon absorptiometry, hormonal and biochemical measurements, which included GH, IGF-I, serum calcium, phosphate, alkaline phosphatase, 1,25 dihydroxy vitamin D and urinary calcium and hydroxyproline excretion. Seven patients were re-studied after IGF-I was suppressed for six months by the somatostatin analog 201-995 (five patients) or pituitary adenomectomy (two patients). BMD was normal in 22 patients and was decreased at one site each in one eugonadal and two hypogonadal patients. BMD was similar between the eugonadal and hypogonadal groups at all sites. Urinary hydroxyproline excretion was equally increased in both groups. There was no correlation between any of the hormonal or biochemical parameters and the age, sex, race and body mass index matched Z-scores of BMD at any site. Following normalization of IGF-I for 6 mo in seven patients, there was no significant change of BMD. We conclude that proximal femoral and lumbar spine BMD is normal in most patients with active acromegaly, including those who are hypogonad. Successful treatment of acromegaly does not result in major short-term changes in BMD.
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PMID:Bone mineral density of the axial skeleton in acromegaly. 151 33

The effect of hyperglycemia on whole body substrate utilization and the metabolic profile of skeletal muscle has been investigated. Eight glucose-tolerant men were infused with somatostatin (S) for 190 min. During the last 120 min of S infusion, glucose was infused to achieve a steady-state plasma level of 26 mmol/l. Biopsies were obtained from the quadriceps femoris muscle immediately before and 35 and 120 min after induction of hyperglycemia. Steady-state glucose disposal during hyperglycemia averaged (+/- SE) 33.8 +/- 3.2 mumol.kg fat-free mass-1.min-1, and approximately 70% of the glucose disposal was accounted for by skeletal muscle. Intracellular glucose increased from 0.9 +/- 0.2 mmol/kg dry wt during S to 9.5 +/- 2.5 during hyperglycemia (P less than 0.01). It was estimated that approximately 35% of the glucose taken up by muscle during 120 min of hyperglycemia was not phosphorylated. Muscle contents of alpha-D-glucose 1,6-diphosphate, D-glucose 6-phosphate, ATP, ADP, and AMP (both of which are based on the phosphocreatine-to-creatine ratio), which have been shown to inhibit hexokinase in vitro, did not change significantly during hyperglycemia, nor were there any significant changes in any of the other postphosphofructokinase intermediates, D-fructose 2,6-diphosphate, and citrate. Hyperglycemia did not alter the fractional activities of glycogen synthase or phosphorylase, nor total phosphorylase activity. However, hyperglycemia resulted in a 55% increase in glycogen synthase-specific activity (P less than 0.01). It is concluded that hyperglycemia results in a marked increase in muscle glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hyperglycemia induces accumulation of glucose in human skeletal muscle. 167 95

Glucokinase was proposed to function as a glucose sensor in pancreatic B-cells, acting possibly as a pacemaker of the rate of glycolysis. Glucose, mannose, and 2-deoxyglucose are good substrates of glucokinase which are easily taken up into B-cells. Glucose and mannose are well-known stimuli of insulin release in mammals and fish. I report here that 2-deoxyglucose is also a strong stimulus of insulin and somatostatin release from the in vitro perfused pancreas (i.e., splenic Brockmann body) of channel catfish (Ictalurus punctatus). This is surprising because the product of the glucokinase-catalyzed phosphorylation of 2-deoxyglucose. 2-deoxyglucose-6-phosphate, cannot be metabolized further at an appreciable rate. 3-O-Methylglucose, which does not bind appreciably to mammalian glucokinase, stimulated neither insulin nor somatostatin release. Glucosamine, which binds tightly to glucokinase but is phosphorylated only at a very low rate, did not stimulate insulin release either, but did cause a small amount of somatostatin to be released. The results suggest that glucose-activated glucokinase itself may serve as a signal molecule in glucose recognition by B- and D-cells.
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PMID:2-Deoxyglucose stimulates the release of insulin and somatostatin from the perfused catfish pancreas. 167 44

Oxytocin (OT) produced a dose-dependent increase in somatostatin, glucagon and insulin release by isolated mouse islets. A small effect on somatostatin release was observed with 0.1 nM-OT, but 1-10 nM-OT was required to affect A- and B- cells significantly. The effects of OT on somatostatin and glucagon release were similar in the presence of 3 mM- and 10 mM-glucose. No change in insulin release was produced by OT in 3 mM-glucose, but a stimulation was still observed in the presence of a maximally effective concentration of glucose (30 mM). The increase in insulin release produced by OT (in 15 mM-glucose) was accompanied by small accelerations of 86Rb and 45Ca efflux from islet cells. Omission of extracellular Ca2+ accentuated the effect of OT on 86Rb efflux, attenuated that on 45Ca efflux, and abolished that on release. OT never inhibited 86Rb efflux. It did not affect the resting potential of B-cells, but slightly increased the Ca2(+)-dependent electrical activity induced by 15 mM-glucose. OT did not affect cyclic AMP levels, but increased inositol phosphate levels in islet cells. It is suggested that the amplification of glucose-induced insulin release that OT produces is due to a stimulation of phosphoinositide metabolism, and presumably an activation of protein kinase C, rather than to a change in cyclic AMP levels or a direct action on the membrane potential. Since OT is present in the pancreas, it is possible that it exerts a neuropeptidergic control of the islet function.
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PMID:Mechanisms of the stimulation of insulin release by oxytocin in normal mouse islets. 167 63


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