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 effects of somatostatin on fasting and absorptive plasma ammonia and amino acids were studied in 12 cirrhotic patients. They received a 6 h intravenous infusion of somatostatin (500 micrograms/h) or saline, starting 90 min before protein feeding. During the fasting period somatostatin significantly reduced plasma ammonia (-18%) and total tryptophan (-39%), increased plasma leucine (+19%), isoleucine (+17%), glutamine (+22%), glycine (+13%), arginine (+14%) and lysine (+12%), and prevented the significant fall of phenylalanine (-8%), tyrosine (-6%), alanine (-8%) and threonine (-9%) seen with saline. The percent changes in ammonia and glutamine concentrations were inversely correlated (r = -80; p less than 0.001) After protein ingestion, somatostatin slowed the maximal plasma increase in ammonia and alpha-nitrogens by at least two hours, but their total 5 h plasma response was not reduced, and even, in some instances, significantly increased (valine, leucine, glutamine, alanine and serine) with respect to saline. The results suggest that in fasting cirrhotics somatostatin reduces plasma ammonia, probably through an impaired intestinal ammoniogenesis from circulating precursors, and inhibits the disposal of branched chain, aromatic (except tryptophan) and gluconeogenic amino acids. Furthermore, it delays, but does not reduce, the plasma increase in nitrogen after protein ingestion.
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PMID:Effects of somatostatin on plasma ammonia and amino acid profile during fasting and after protein feeding in cirrhotic patients. 287 93

We synthesized a series of octapeptide analogs of somatostatin, containing N-terminal tryptophan or another amino acid followed by the hexapeptide sequences Cys-Phe-D-Trp-Lys-Thr-Cys or Cys-Tyr-D-Trp-Lys-Val-Cys and a C-terminal threoninamide or tryptophanamide. After purification by HPLC, the inhibitory activities of these analogs on the release of growth hormone (somatotropin) in rats were determined in vivo. The eight octapeptides with an N-terminal tryptophan residue were found to have a greater inhibitory effect than somatostatin. The most potent of these analogs, D-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2, was 94.3 times more active than somatostatin. The other analogs, in order of decreasing potency, were Ac-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2, D-Trp(For)-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2, D-Trp-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2, Ac-Trp(For)-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2, Ac-Trp-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2, D-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Trp-NH2, and D-Trp-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2. The growth hormone inhibitory activity of these analogs was from 53.7 to 11.6 times greater than that of somatostatin. The octapeptides containing D- or L-tryptophan at the N-terminus, phenylalanine at position 3, and threonine at position 6 exhibited a greater inhibitory effect on growth hormone release than that of the analogs with tyrosine and valine at positions 3 and 6, respectively. Substitution of D-tryptophan for D-phenylalanine at the N-terminus in the octapeptide containing phenylalanine in the third, threonine in the sixth, and threoninamide in the C-terminal position also increased the growth hormone-release inhibitory activity. Time-course assay showed that D-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2 (RC-98-I), in a dose of 1 microgram/kg of body weight, inhibited the release of growth hormone for at least 3 hr. In view of their high activity and prolonged duration of action, some of these analogs could be useful clinically.
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PMID:Superactive octapeptide somatostatin analogs containing tryptophan at position 1. 288 20

We describe a family from Japan displaying the mutant insulin syndrome with hyperinsulinaemia and an increased insulin: C-peptide molar ratio. Serum insulin isolated from several family members showed reduced in vitro biological activity, and analysis by high performance liquid chromatography revealed a peak co-eluting with human insulin and a second species of increased hydrophobicity co-migrating with the previously reported Insulin Wakayama. The insulin genes from the propositus were cloned and sequenced, revealing one normal allele; the second allele, encoding a leucine for valine amino acid substitution at position 3 of the insulin A chain, was similar to that previously described for Insulin Wakayama. Synthesized [LeuA3] insulin showed 0.14% of receptor binding activity on rat adipocytes and a 10-fold prolonged half-life in a somatostatin-infused dog compared with human insulin. The finding of the same mutant gene in two unrelated Japanese families suggests that Insulin Wakayama may be discovered in additional Japanese families with hyperinsulinaemia and/or diabetes.
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PMID:Insulin Wakayama: familial mutant insulin syndrome in Japan. 355 28

1. Somatostatin (SRIF, somatotropin release inhibiting factor), at a concentration of 2 x 10(-8) M (32 ng/ml) decreased the rat of alanine release (approximately 45%) and increased glutamine release (approximately 30%) in in vitro preprations of m. extensor digitorum longus (EDL) muscle from 35--40 day old Wistar rats. These effects of SRIF were observed under both aerobic and anaerobic conditions. 2. SRIF increased the formation of 14CO2 from alanine but not from glutamine, glutamate, leucine, isoleucine or valine. 3. The incorporation of alanine, glutamine, glutamate, leucine, isoleucine and valine into muscle protein was unaffected by the presence of SRIF.
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PMID:The effect of somatostatin (SRIF) on the release of amino acids from skeletal muscle. 610 70

Tryptophan is readily oxidized to oxindolylalanine (2-hydroxytryptophan) in good yield on treatment in acetic acid solution with a mixture of dimethyl sulfoxide (DMSO) and concentrated aqueous HCl at room temperature. Other sulfoxides can be used in combination with HCl; for example, methionine sulfoxide reacts with an equimolar amount of tryptophan to give high yields of methionine and oxindolylalanine. Methionine and cysteine are quantitatively oxidized by DMSO/HCl to methionine sulfoxide and cystine, respectively. The tryptophan containing peptides LRF (luteinizing hormone-releasing factor), somatostatin, valine-gramicidin A and ACTH 1-24 were each treated with the DMSO/HCl reagent in acetic acid solution and the corresponding oxindolylalanine-derivatives isolated in over 90% yield after chromatography. The identity and purity of the derivatives were established on the basis of ultraviolet spectral characteristics and quantitative amino acid analysis of the oxindolylalanine content of acid hydrolyzates of the oxidized peptides with 3N-p-toluenesulfonic acid at 110 degrees for 24 h. The results indicate that modification of tryptophan peptides with DMSO/HCl provides a useful procedure, which seems superior to previously used reagents. In addition, the method could be well applied to other indoles of biological and pharmacological interest.
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PMID:Oxidation of tryptophan to oxindolylalanine by dimethyl sulfoxide-hydrochloric acid. Selective modification of tryptophan containing peptides. 615 58

The effect of the dopamine agonist bromocriptine and the somatostatin analog SMS 201-995 on growth of 12 human somatotrophic and 13 non-functioning adenoma cell cultures was investigated. When adenoma cells were maintained in medium supplemented with 5% fetal calf serum, cell counts of 10 of 12 somatotrophic cultures increased to 145 +/- 6 and 171 +/- 9% (mean +/- SD) and in 12 of 13 non-functioning cell cultures up to 125 +/- 12 and 217 +/- 15% after 3 days of incubation. In most cases bromocriptine and SMS 201-995 dose dependently (1 nmol/l to 10 mumol/l) inhibited adenoma cell growth but there was only (1, 10 mumol/l) a significant inhibitory effect at high doses of both drugs. A 1 mumol/l concentration of bromocriptine decreased cell counts of 5 of 12 somatotrophic cell cultures (range 84 +/- 3 to 76 +/- 6% vs control = 100%) and in 5 of 13 non-functioning cell cultures (range 85 +/- 4 to 71 +/- 7%). A 10 mumol/l concentration of bromocriptine decreased cell counts in all 12 somatotrophic (range 87 +/- 1 to 61 +/- 8%) and in 12 of 13 non-functioning adenoma cultures (range 87 +/- 6 to 57 +/- 3%). Bromocriptine specifically inhibited growth because its effect could be reversed by the dopamine D2-receptor antagonist haloperidol. Both 1 and 10 mumol/l SMS 201-995 significantly decreased cell counts in three of six somatotrophic (87 +/- 3 to 38 +/- 3%) cell cultures. In two of five cases growth of non-functioning adenoma cultures was suppressed by 1 mumol/l SMS 201-995, and in four of five cases by 10 mumol/l (86 +/- 3 to 74 +/- 4%). The growth inhibitory effect of both bromocriptine and SMS 201-995 was not just due to an effect on growth of fibroblasts contaminating the adenoma cell cultures, because it could be observed also when adenoma cells were maintained in a D-valine-supplemented medium that suppresses fibroblast growth. In summary, both bromocriptine and SMS 201-995 at high doses were able to inhibit cell growth of cultured somatotrophic and non-functioning adenomas in vitro. However, the mechanism of this inhibitory effect is not yet well understood.
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PMID:Effect of bromocriptine and SMS 201-995 on growth of human somatotrophic and non-functioning pituitary adenoma cells in vitro. 812 83

Several studies have shown that exogenous human growth hormone (HGH) exerts an anabolic effect on protein metabolism in surgical patients with mild or moderate catabolism. However, contradictory results have been demonstrated in polytrauma patients where HGH did not improve protein metabolism. Aim of this study was to evaluate whether the pharmacokinetics of recombinant biosynthetic human GH (r-HGH) are altered in critically ill patients. After an overnight fast, r-HGH was infused at a rate of 460 micrograms/h/kg/bw during 120 min to five intensive care unit (ICU) patients. The patients were catabolic (nitrogen balance -11 +/- 0.5), showed normal liver function, and only one patient had a slightly impaired kidney function (creatinine > 1.5 mg/dl). Endogenous GH secretion was suppressed by continuous infusion of 50 micrograms/m2/h somatostatin. From plasma GH curves, elimination half life (t1/2kle), whole body clearance (Cltot) and steady state distribution space (DS) were calculated in an open two compartment model. Additionally, the effects of r-HGH infusion on plasma insulin, glucagon and amino acid concentrations were evaluated. T1/2kle was 19.6 +/- 2.3 min, Cltot 2.9 +/- 0.4 ml/kg/bw/min and DS 76.4 +/- 3.8 ml/kg/bw for 90 min. The plasma levels of total amino acids including the branched chain amino acids valine, leucine and isoleucine and of glutamine were significantly higher during r-HGH infusion than during the basal and somatostatin periods. In conclusion, the elimination of r-HGH in catabolic ICU patients is not different from that of healthy volunteers.
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PMID:Human growth hormone kinetics in critically ill patients. 876 7

Recent studies have indicated that deposition of beta amyloid peptide in the brains of patients with senile dementia of the Alzheimer type (SDAT) is a consequence of abnormal processing of the beta amyloid protein precursor. In addition, reduced concentrations of various peptides have been measured in post-mortem brain tissue and cerebrospinal fluid (CSF) of patients with SDAT. We determined concentrations of the peptides derived from prepro-vasoactive intestinal peptide (VIP)--peptide histidine methionine-27 (PHM-27), peptide histidine valine (PHV) and VIP--and peptides derived from prepro-somatostatin (prepro-SS), SS-14 and SS-28, in CSF of patients with SDAT by radioimmunoassay combined with high performance liquid chromatography. We found significantly reduced levels of total PHM-immunoreactivity (IR) and PHV, and unaltered levels of PHM-27 and VIP in SDAT, compared with those in controls. Total SS-IR and SS-28 concentrations were significantly reduced in SDAT, while SS-14 levels did not differ from those of controls. These results suggest that an altered processing of the prepro-peptides of VIP and SS may occur in SDAT and that these alterations might have a significant role in the pathogenesis of SDAT.
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PMID:Low cerebrospinal fluid concentrations of peptide histidine valine and somatostatin-28 in Alzheimer's disease: altered processing of prepro-vasoactive intestinal peptide and prepro-somatostatin. 883 59

Human presenilin-1 (PS1) mutations are associated with the incidence of familial Alzheimer's disease. The present study evaluated the behavioral and neurochemical effects of the L235P mutation (substitution of leucine by proline at codon 235) of the human PS1 gene, which has been linked to a form of early-onset Alzheimer's disease. Except for a significant increase in the production of beta-amyloid-42, the mutant mice did not show any overt signs of Alzheimer-like neuropathology in the form of plaque formation, changes in choline acetyltransferase activity, or somatostatin content in the brain. Cognitive assays indicated that the mutation did not affect the acquisition or reversal of a spatial reference memory task in the water maze or performance on a spatial working memory task. In contrast, L235P PS1 transgenic mice exhibited a significant impairment in a test of spontaneous object recognition. This dissociation is suggestive of a preferential impairment of the extrahippocampal memory system and is consistent with what has been reported in another pathological mutation (substitution of leucine by valine at codon 286) of the PS1 gene.
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PMID:Behavioral and neurochemical characterization of transgenic mice carrying the human presenilin-1 gene with or without the leucine-to-proline mutation at codon 235. 1455 9

Mass spectrometry of HPLC-purified porcine glucagon-like peptide-2 (pGLP-2)(1) revealed a 35 amino acid sequence with C-terminal Ser and Leu, in contrast to the 33 amino acids of human, cow, rat and mouse GLP-2. Synthetic pGLP-2 stimulated cAMP-production in COS-7 cells expressing human GLP-2 (hGLP-2) receptor with the same potency and efficacy as hGLP-2. In anesthetized pigs (n=9) given intravenous pGLP-2 infusions, the half life (t1/2) of intact pGLP-2 (8.4+/-0.9 min) was shorter (p<0.01) than that of the primary metabolite pGLP-2 (3-35) (34.0+/-5.2 min), generated by dipeptidyl peptidase-4 (DPP-4) cleavage. Adding the DPP-4 inhibitor valine-pyrrolidide prolonged t1/2 of intact pGLP-2 (p<0.05). The metabolic clearance rate (MCR) of intact pGLP-2 (23.9+/-3.82 mL/(kg x min)) was greater (p<0.0001) than that of pGLP-2 (3-35) (6.36+/-1.45 mL/(kg x min)) and larger than the previously reported MCR of hGLP-2 in pig. The MCR of intact pGLP-2 was reduced by valine-pyrrolidide (p<0.05), but was still greater than that of intact hGLP-2 previously reported. In the isolated perfused porcine pancreas, pGLP-2 stimulated glucagon release (p<0.05), but had no effect on insulin or somatostatin release. Exocrine secretion was unaffected and there was no apparent vasoactive effect. In mice (n=8), both subcutaneous hGLP-2 and pGLP-2 given twice daily for 10 days, significantly and equally increased small intestinal weight, length and cross-sectional area of proximal ileum. In conclusion, pGLP-2 and hGLP-2 have similar effects in vivo and in vitro in spite of the structural differences. However, pGLP-2 is cleared more rapidly in pigs than hGLP-2.
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PMID:Porcine glucagon-like peptide-2: structure, signaling, metabolism and effects. 1816 96


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