Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eighty-one percent of 339 alcoholics participating in a research program were found to have associated mental disorders. Alcoholics with onset of heavy drinking before 20 years of age had significantly more antisocial personality traits, drug abuse, bipolar disorder, panic disorder, suicide attempts, and paternal alcoholism than alcoholics with onset after age 20 years. Alcoholics with onset before and after 20 years of age also differed significantly from each other for cerebrospinal fluid concentrations of diazepam-binding inhibitor and somatostatin. These results support the notion that age of onset may delineate subgroups of alcoholics with significant clinical and neurochemical differences.
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PMID:Mental disorders among alcoholics. Relationship to age of onset and cerebrospinal fluid neuropeptides. 167 94

Porcine diazepam-binding inhibitor (pDBI) is a novel peptide that has been isolated from the small bowel of the pig, and that occurs also in the islet D-cells. We have studied its effects on hormone release in vitro from the endocrine pancreas of the rat. In isolated islets, pDBI (10(-9)-10(-6)M) did not affect basal insulin release at 3.3 mM glucose, whereas stimulated release at 8.3 mM glucose was dose-dependently suppressed by 32-69% (P less than 0.01). Furthermore, insulin secretion stimulated by either 16.7 mM glucose or 1 mM IBMX (3-isobutyl-1-methylxanthine) or 1 micrograms/ml glibenclamide was suppressed by pDBI at 10(-8) M (by 28-30%, P less than 0.05) and 10(-7) M (by 43-47%, P less than 0.01). In contrast, islet insulin secretion induced by 20 mM arginine was unaffected by these concentrations of pDBI. In the perfused rat pancreas, pDBI (10(-8) M) enhanced by 30% (P less than 0.05) the first phase (0-5 min) of arginine-stimulated insulin release, whereas the second phase (5-20 min) was unchanged. Moreover, pDBI suppressed by 28% (P less than 0.05) the second phase of arginine-induced glucagon release. Arginine-induced somatostatin release was not significantly affected by the peptide. Since pDBI immunoreactivity has been localized also to islet D-cells, the present results suggest that pDBI may act as a local modulator of islet hormone release.
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PMID:Effects of porcine diazepam-binding inhibitor on insulin and glucagon secretion in vitro from the rat endocrine pancreas. 169 50

Regulation of blood glucose homeostasis is complex. Its major hormonal regulators include insulin, glucagon and somatostatin from the endocrine pancreas. Secretion of these hormones is controlled predominantly by the supply of nutrients in the circulation but also by nerve signals and other peptides. Thus, it is likely that peptides, released from cells of the gut or endocrine pancreas or from peptidergic nerves, affect glucose homeostasis by modulating the secretion of insulin, glucagon and somatostatin. When searching for novel gut peptides with such effects, diazepam binding inhibitor (DBI) was isolated from the porcine small intestine. By immunocytochemistry, DBI has been demonstrated to occur not only in the gut but also in endocrine cells of the pancreatic islets, namely in the somatostatin-producing D-cells in pig and man, and in the glucagon-producing A-cells in rat. Porcine DBI (pDBI; 10(-8)-10(-7) M) has been shown to suppress glucose-stimulated release of insulin from both isolated islets and perfused pancreas of the rat. Furthermore, secretion of insulin stimulated by either the sulfonylurea glibenclamide or the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), was inhibited by the peptide. In contrast, arginine-induced release of insulin was unaffected by pDBI. Moreover, pDBI decreased arginine-induced release of glucagon from the perfused rat pancreas, whereas release of somatostatin was unchanged. Notably, rat DBI, structurally identical with rat acyl-CoA-binding protein, has also been demonstrated to inhibit glucose-stimulated release of insulin in the rat, both in vivo and in vitro. Long-term exposure of cultured fetal rat islets to pDBI (10(-8) M) significantly decreased the synthesis of DNA in islet cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diazepam binding inhibitor and the endocrine pancreas. 178 37

Neuropeptides were examined in relation to suicidal behavior and its repetition in depression. There were no significant differences between depressed patients who had or had not attempted suicide for cerebrospinal fluid (CSF) concentrations of neuropeptide Y, somatostatin, diazepam-binding inhibitor, GABA, or corticotropin releasing hormone. A 5-year follow-up was carried out. There were no significant differences between depressed patients who did or did not reattempt suicide during the follow-up or who had never attempted for CSF concentrations of any of the neuropeptides measured. These negative results suggest that these neuropeptides are probably not major determinants of suicidal behavior or its repetition in depression.
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PMID:Neuropeptides in relation to suicidal behavior in depression. 790 97

Exocrine pancreatic secretion is regulated by hormone-hormonal and neural-hormonal interactions involving several regulatory peptides and neurotransmitter from the gut, the pancreas and the vagus nerve. The roles of the gastrointestinal peptides including secretin, CCK, neurotensin, motilin, PYY and pancreatic islet hormones including insulin, pancreatic polypeptide and somatostatin have been established. Interactions among secretin, CCK and neurotensin produce synergistic stimulatory effect. Motilin modulates the cyclic pattern of pancreatic secretion while local insulin provides a permissive role for the action of secretin and CCK at physiological concentration. Somatostatin, PYY and pancreatic polypeptide are inhibitory regulators, acting either on the release of secretin and CCK or on the action of the two stimulatory hormones. The vagal afferent-efferent pathway mediates the actions of many of these regulatory peptides, particularly of secretin and CCK. Acetylcholine and nitric oxide are the neurotransmitters known to mediate the actions of secretin and CCK. Serotonin (5-HT) released from enterochromaffin cells in the intestinal mucosa and nerve terminals of the enteric nervous system and intrapancreatic nerves may be involved in both stimulatory and inhibitory mechanism through its various receptor subtypes. 5-HT also mediates the action of secretin and CCK. The regulatory roles of neuropeptides, PACP and GRP, are now established, whereas those of others are being uncovered. Pancreatic juice provides both positive and negative feedback regulation of pancreatic secretion through mediation of both secretin- and CCK-releasing peptides. Three CCK-releasing peptides have been purified: monitor peptide from pancreatic juice, diazepam-binding inhibitor from porcine intestine, and luminal CCK-releasing factor from rat intestinal secretion. All have been shown to stimulate CCK release and pancreatic enzyme secretion. Pancreatic phospholipase A2 from pancreatic juice and intestinal secretion appears to function as a secretin-releasing peptide. However, the detailed map of neurohormonal regulatory pathways of exocrine pancreatic secretion is yet to be constructed.
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PMID:Neural hormonal regulation of exocrine pancreatic secretion. 1212 Feb 11

Endozepines, a family of regulatory peptides related to diazepam-binding inhibitor (DBI), are synthesized and released by astroglial cells. Because rat astrocytes express various subtypes of somatostatin receptors (sst), we have investigated the effect of somatostatin on DBI mRNA level and endozepine secretion in rat astrocytes in secondary culture. Somatostatin reduced in a concentration-dependent manner the level of DBI mRNA in cultured astrocytes. This inhibitory effect was mimicked by the selective sst4 receptor agonist L803-087 but not by the selective sst1, sst2 and sst3 receptor agonists L779-591, L779-976 and L797-778, respectively. Somatostatin was unable to further reduce DBI mRNA level in the presence of the MEK inhibitor U0126. Somatostatin and the sst1, sst2 and sst4 receptor agonists induced a concentration-dependent inhibition of endozepine release. Somatostatin and the sst1, sst2 and sst4 receptor agonists also inhibited cAMP formation dose-dependently. In addition, somatostatin reduced forskolin-induced endozepine release. H89 mimicked the inhibitory effect of somatostatin on endozepine secretion. In contrast the PLC inhibitor U73122, the PKC activator PMA and the PKC inhibitor calphostin C had no effect on somatostatin-induced inhibition of endozepine release. The present data demonstrate that somatostatin reduces DBI mRNA level mainly through activation of sst4 receptors negatively coupled to the MAPK pathway, and inhibits endozepine release through activation of sst1, sst2 and sst4 receptors negatively coupled to the adenylyl cyclase/PKA pathway.
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PMID:Somatostatin down-regulates the expression and release of endozepines from cultured rat astrocytes via distinct receptor subtypes. 1603 15

Astroglial cells synthesize and release endozepines, a family of neuropeptides derived from diazepam-binding inhibitor (DBI). The authors have recently shown that beta-amyloid peptide (Abeta) stimulates DBI gene expression and endozepine release. The purpose of this study was to determine the mechanism of action of Abeta in cultured rat astrocytes. Abeta(25-35) and the N-formyl peptide receptor (FPR) agonist N-formyl-Met-Leu-Phe (fMLF) increased the secretion of endozepines in a dose-dependent manner with EC(50) value of approximately 2 microM. The stimulatory effects of Abeta(25-35) and the FPR agonists fMLF and N-formyl-Met-Met-Met (fMMM) on endozepine release were abrogated by the FPR antagonist N-t-Boc-Phe-Leu-Phe-Leu-Phe. In contrast, Abeta(25-35) increased DBI mRNA expression through a FPR-independent mechanism. Abeta(25-35) induced a transient stimulation of cAMP formation and a sustained activation of polyphosphoinositide turnover. The stimulatory effect of Abeta(25-35) on endozepine release was blocked by the adenylyl cyclase inhibitor somatostatin, the protein kinase A (PKA) inhibitor H89, the phospholipase C inhibitor U73122, the protein kinase C (PKC) inhibitor chelerythrine and the ATP binding cassette transporter blocker glyburide. Taken together, these data demonstrate for the first time that Abeta(25-35) stimulates endozepine release from rat astrocytes through a FPR receptor positively coupled to PKA and PKC.
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PMID:Beta-amyloid peptide stimulates endozepine release in cultured rat astrocytes through activation of N-formyl peptide receptors. 1851 51

Cerebrospinal fluid (CSF) neurohumors reflect central nervous system physiology in a way that peripheral indices can not. We reviewed clinical studies of CSF biogenic amines and neurohormones in alcohol misusers during various stages of withdrawal or abstinence and found them difficult to compare because of highly variable experimental methods, reliance on single time collections (lumbar punctures) that fail to control for potential stress-induced effects of the procedure, lack of control for tobacco use, and a paucity of non-alcoholmisusing controls. However, taken together, the data thus far show that a variety of neuroactive substances are reduced in concentration in the CSF of some alcohol misusers. Low CSF levels of corticotropinreleasing hormone, beta-endorphin, norepinephrine, diazepam-binding inhibitor, 5-hydroxyindoleacetic acid and somatostatin have all been reported. Whether the decreased CSF levels of these neurohormones and neurotransmitters are a cause or consequence of alcoholism has not been determined. In fact, further studies using serial or continuous CSF sampling techniques with homogeneous, better-characterized patients and normal volunteers are still needed to establish the precise CSF neurochemical abnormalities in alcohol misusers.
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PMID:Cerebrospinal fluid neuroendocrinology of alcohol misusers. 2673 45

The cellular distribution of a novel porcine peptide, diazepam-binding inhibitor (DBI), was immunohistochemically mapped in the human and porcine gastrointestinal tract and pancreas. Using a rabbit antiserum, raised against porcine DBI, immunoreactive epithelial cells were found in the gastric antrum and duodenal mucosa and in the parenchymal cells of the islets of Langerhans of both species. The immunoreactivity could not be absorbed by high concentrations of insulin, somatostatin (SS-14, SS-28), glucagon, or pancreatic polypeptide but was abolished by porcine DBI. Using semithin, consecutive sections, the immunoreactive intestinal and islet cells were found to be identical to the somatostatin-producing D cells. Since it has been shown that porcine DBI interferes with the secretion of insulin, the peptide may act as a modulator of islet hormone release, possibly in a paracrine manner.
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PMID:Porcine diazepam-binding inhibitor is immunohistochemically colocalized with somatostatin in the D cells of human and porcine gastrointestinal tract and in pancreatic islet cells. 3235 45