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)

Studies in female ob/ob mice demonstrated diabetogenic properties of human growth hormone (somatotropin) and of a fragment generated therefrom by controlled digestion with pepsin; both the fragment and parent growth hormone produce long-term effects on carbohydrate metabolism; in acute glucose tolerance tests, only the fragment is active. Two nonacidic diabetogenic fractions have been separated from inactive fractions by chromatography on Bio-Gel P-6 followed by ion exchange chromatography at pH 4.3 and gel filtration on Bio-Gel P-2 and/or Sephadex G25; these active fractions exhibited multiple NH2-terminal (Lys, Phe, Leu, and Tyr). Fraction CD has these characteristics: (i) It induces glucose intolerance in fasting female ob/ob mice when injected subcutaneously in a divided dose, 15 min before and concurrently with glucose; mice injected with sufficient peptide exhibit elevated fasting glucose levels as long as 7 months after a single glucose tolerance test. (ii) It is a peptide smaller than that reported to stimulate body growth, but larger than somatostatin. This peptide, as reported earlier, does not crossreact with antiserum to human growth hormone in radioimmunoassay.
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PMID:Diabetogenic peptide from human growth hormone: partial purification from peptic digest and long-term action in ob/ob mice. 107 22

Two distinct somatostatin precursors are synthesized in anglerfish (AF) islets. In addition to a precursor which has somatostatin 14 (SS-14) as a C-terminal cleavage product, a precursor which contains at its C-terminus [Tyr7, Gly10] SS-14 as a potential cleavage product is also synthesized. However, even though an Arg-Lys pair is located immediately N-terminal to Ala1 of the C-terminal tetradecapeptide, [Tyr7, Gly10]SS-14 was not found in significant amounts in extracts of AF islets. Instead, a 28 residue peptide having [Tyr7, Gly10]SS-14 (AF SS-28) at its C-terminus was found to be a primary cleavage product of this form of pro-SS. A question which arises from these observations is whether the differential cleavage of pro-SS-14 (PSS-I) and pro-SS-28 (PSS-II) is the result of differences in primary and/or secondary structure of the two precursors which in turn modulate the activity of the same converting enzyme, or whether separate cleavage enzymes exist for each precursor. Experiments were designed to address this question. Microsomes (M) and secretory granules (SG) were isolated from AF pancreatic islets. Fraction purity was monitored by RIA for islet hormones, and by assays for plasma membrane and lysosomal enzymes. The ability of lysed M and SG preparations to mediate conversion of radiolabeled islet prohormones to products was monitored by gel filtration and HPLC analysis of the products. The pH optimum for converting activity in M and SG was found to be near 5.0. Incubations in the presence of selective proteinase inhibitors and prohormones containing Arg and Lys analogs demonstrated that a cysteine proteinase(s) which cleaves at basic amino acid residues is involved in granule-mediated conversion. A significant proportion of the converting activity in granules was found to co-precipitate with SG membranes. Washing these membranes with 1M KC1 resulted in dissociation of most of the converting activity from the membranes suggesting that the proteinase(s) involved is membrane-associated. The processing activities for proinsulin and pro-SS-28 which were observed in SG were also found to be active, and membrane-associated, in M. However, converting activity for pro-SS-14 was found only in SG. Much of the PSS-I to SS-14 processing activity was membrane-associated in SG. By contrast, pro-SS-28 converting activity in SG was entirely soluble. These results suggest that two or more separate enzymes are involved in processing pro-SS-14 and pro-SS-28 and that these enzymes have differential activity in M and SG.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Post-translational processing of anglerfish islet somatostatin precursors. 286 27

Using a radioimmunoassay with labeled synthetic tetradecapeptide somatostatin, a large amount of immunoreactive somatostatin was found in the principal pancreatic islet of the channel catfish (Ictalurus punctata). The purpose of these experiments was to isolate and characterize the somatostatin-like material. Extracts of islets were chromatographed on a Bio-Gel P-30 column, and over 90% of the immunoreactive somatostatin migrated with proteins at least twice the size of synthetic tetradecapeptide somatostatin. This fraction was further purified by ion-exchange chromatography on carboxymethyl-cellulose and DEAE-cellulose columns. Two peptides were obtained with identical immunoreactivity, which was approximately 25% that of the synthetic somatostatin. Each peptide was judged to be >95% pure by thin-layer electrophoresis, polyacrylamide gel electrophoresis at pH 8.9, and highpressure liquid chromatography. Further criteria of purity included amino-terminal analysis of fraction IV yielding only aspartic acid. A total of 1.3 mg of fraction II, and 3.8 mg of fraction IV somatostatin-like peptides were obtained from 10 g of fresh frozen islets. Characterization of the two peptides revealed both peptides slightly more acidic than synthetic tetradecapeptide somatostatin. Fraction II had an isoelectric point of 8.0-8.3, and fraction IV 8.3-9.0. Molecular weight estimation by sodium dodecyl sulfate-urea polyacrylamide gel electrophoresis revealed similar mobility of both peptides, between pancreatic polypeptide (mol wt 4,500) and glucagon (mol wt 3,500). The mobility was not altered by reduction, and was approximately twice the size of synthetic tetradecapeptide somatostatin (mol wt 1,800). This confirmed that the peptides were single polypeptide chains and not aggregates, or somatostatin bound to larger proteins. Molecular weight determination by gel filtration chromatography on Bio-Gel P-6 in 8 M urea gave an estimated mol wt of 3,700. Amino acid analysis of the two immunoreactive somatostatins indicated that they were very similar in composition. Both pancreatic somatostatins (1 muM) had full biological activity relative to synthetic somatostatin measured as inhibition of growth hormone release from rat anterior pituitary cells.
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PMID:Isolation and characterization of immunoreactive somatostatin from fish pancreatic islets. 610 73

The present study was conducted to examine roles of brain monoamines and opioid peptides in growth hormone (GH) secretion in unanesthetized, freely behaving rats. The administration of chlorpromazine (CPZ, 300 microgram/100 g, i.v.), an antagonist of brain monoamines, to rats that were passively immunized with antiserum to somatostatin immediately lowered plasma GH levels and inhibited episodic GH secretion. An intraventricular injection of beta-endorphin (3.5 microgram) stimulated GH secretion. This effect was completely inhibited by the prior administration of naloxone (100 microgram/100 g, i.v.), a specific antagonist of opioid peptides, but not by CPZ. In addition, the administration of naloxone did not inhibit episodic GH secretion. The results suggest that CPZ inhibits episodic GH secretion via a factor(s) other than somatostatin. It is also inferred that brain monoamines, but not opioid peptides, play major roles in the regulation of episodic GH secretion in rats.
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PMID:Effects of chlorpromazine and naloxone on growth hormone secretion in rats. 610 6

Fetal leucine oxidation rate is elevated during fasting of the ewe. Euglycemic hyperinsulinemia causes the leucine oxidation rate to decline. However, it is unclear whether this is a direct effect of insulin or is secondary to increased insulin-mediated glucose utilization. To better delineate the mechanism of decreased oxidation, we suppressed fetal insulin secretion by somatostatin infusion. Glucose was infused at a variable rate to achieve glucose concentrations 125 and 150% of basal. Leucine rate of appearance (Ra) was determined by infusion of [15N, 1-13C]leucine. Fraction of leucine appearance oxidized was determined by [1-14C]leucine infusion and determination of fetal 14CO2 excretion. Each fetus was studied during ad libitum maternal feeding and after a 5-day complete maternal fast. Changes were noted in fetal leucine oxidation, which declined from 8.4 +/- 1.2 to 5.0 +/- 0.8 mumol/min in the fed state during glucose infusion. Basal leucine oxidation was elevated during fasting (11 +/- 1.5 mumol/min, P < 0.05) and declined to 8.0 +/- 1.4 mumol/min during glucose infusion (P = 0.056). Leucine carbon Ra was unchanged by fasting and by glucose infusion; leucine nitrogen Ra declined in the fed state only. Leucine oxidation was inversely correlated with glucose concentration (oxidation = 12-0.26 x glucose concentration, r = 0.42, P = 0.004). Leucine oxidation was not correlated with insulin concentration (r = 0.2). Changes in fetal glucose concentration may alter the pattern of utilization of essential amino acids, independent of changes in insulin and insulin-mediated glucose utilization rate.
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PMID:Increased fetal glucose concentration decreases ovine fetal leucine oxidation independent of insulin. 790 97