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 response of the pancreatic islet A- and B-cells after long-standing (eight years) pancreatic duct occlusion by prolamine, and subsequently developed acinar atrophy, was studied in five beagles, and the results compared with those in six sham-operated dogs. Intravenous arginine infusion (A-cell stimulation) and a combined oral glucose and intravenous tolbutamide and glucagon infusion (B-cell stimulation) were carried out in each dog. Complete abolition of acinar function after duct occlusion was documented by the negative paraaminobenzoic acid test. In contrast, in plasma, baseline values of glucose, alpha-amino-nitrogen, insulin, glucagon, glucagon-like immunoreactivity, somatostatin-like immunoreactivity, and pancreatic polypeptide did not differ between the experimental groups. During B-cell stimulation dogs with occluded ducts had significantly reduced insulin, reduced glucagon, and reduced second phase pancreatic polypeptide compared with controls. Integrated insulin and pancreatic polypeptide were also reduced in dogs with occluded ducts. In both groups plasma and integrated values of glucose and somatostatin-like immunoreactivity did not differ. During the A-cell stimulation period dogs with occluded ducts had significantly raised alpha-amino-nitrogen but unchanged glucose and reduced insulin concentrations; in both groups the arginine-induced rise in glucagon was similar, although it was delayed in the experimental group. In the latter, integrated alpha-amino-nitrogen was raised, but integrated glucose and hormones were unchanged. We conclude that a previously intact dog pancreas that has been atrophied by duct occlusion, may be able to maintain euglycaemia for several years. There may be a complex interplay of changes induced by duct occlusion at the level of the pancreatic islets and elsewhere, which compensate for moderate insulinopenia.
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PMID:Maximal stimulation of pancreatic islet B-cells, and A-cell response to arginine, in dogs with longterm pancreatic acinar atrophy. 167 47

We have investigated the effect of a high concentration (750 nM) of synthetic amidated rat amylin on unstimulated somatostatin and insulin secretion as well as on the response of these hormones to arginine. Amylin consistently reduced insulin output but it did not significantly modify somatostatin release. These findings indicate that the inhibitory effect of amylin on insulin secretion is not mediated by a D-cell paracrine effect.
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PMID:Inhibition of insulin release by amylin is not mediated by changes in somatostatin output. 167 49

Amylin is a pancreatic islet beta-cell peptide hormone which modulates carbohydrate metabolism in skeletal muscle and liver, and could contribute to impaired insulin sensitivity in Type II diabetes. Here we report the first description of amylin secretion from isolated beta-cells. We measured amylin secretion from HIT T15 beta-cells exposed to glucose, arginine, glucagon, somatostatin, tolbutamide, glyburide, or metformin. With the exception of glucagon at concentrations above 1 microM, all compounds induced parallel, dose-dependent changes in secretion of amylin and insulin. We conclude that: 1) insulin and amylin are co-secreted from islet beta-cells; (2) nutrient secretagogues and peptide modulators exert direct effects on beta-cells to alter amylin and insulin secretion; (3) most modulators of islet beta-cell secretion alter amylin and insulin in parallel, but differential secretion can occur; and (4) HIT cell line is a useful model in which to study amylin metabolism.
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PMID:Co-secretion of amylin and insulin from cultured islet beta-cells: modulation by nutrient secretagogues, islet hormones and hypoglycemic agents. 167 26

The identification of pancreastatin in pancreatic extracts prompted the investigation of its effects on islet cell function. However, in most of the investigations to date, pig pancreastatin was tested in heterologous species. Since there is great interspecies variability in the amino acid sequence of pancreastatin, we have investigated the influence of rat pancreastatin on insulin, glucagon and somatostatin secretion in a homologous animal model, namely the perfused rat pancreas. During 5.5 mM glucose infusion, pancreastatin (40 nM) inhibited insulin secretion (ca. 40%, P less than 0.025) as well as the insulin responses to 10 mM arginine (ca. 50%, P less than 0.025) and to 1 nM vasoactive intestinal polypeptide (ca. 50%; P less than 0.05). Pancreastatin failed to significantly modify glucagon or somatostatin release under any of the above experimental conditions. In addition, a lower pancreastatin concentration (15.7 nM) markedly suppressed the insulin release evoked by 11 mM glucose (ca. 85%, P less than 0.05). Our present observations reinforce the concept that pancreastatin is an effective inhibitor of insulin secretion, influencing the B-cell function directly and not through an A-cell or D-cell paracrine effect.
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PMID:Homologous pancreastatin inhibits insulin secretion without affecting glucagon and somatostatin release in the perfused rat pancreas. 168 69

We have reported the potent inhibitory effect of cyclosporine on glucose-induced insulin release in in vitro perfused pancreases. Suppression of both phases of release indicates inhibition of secretion and synthesis. Further studies were performed to examine the effect of high extracellular Ca2+ (4.875 mM). High Ca2+ failed to potentiate release in CsA-treated pancreases, thus we are focusing on the integrity of Ca(2+)-dependent signals in the beta cell. In this study, four groups of pancreases were perfused at 16.7 mM glucose: Control +/- somatostatin (SRIF) and CsA-treated +/- SRIF (60 nM). In control rats, the total 2-hr release decreased 40% with SRIF, from 42.7 +/- 5.5 to 25.5 +/- 3.9 micrograms/300 g body weight (P less than .05). In CsA-treated rats, release decreased 55% with SRIF, from 8.9 +/- 1.1 to 4.0 +/- 0.6 micrograms/300 g body weight. Further, at every time point of these CsA-treated rats, there was approximately 15% greater inhibition by SRIF than in controls. Pancreatic insulin contents were determined, indicating marked depletion of insulin stores in CsA-treated rats (190 +/- 9 vs. 76 +/- 5 micrograms/300 g body weight, P less than .01). Arginine-stimulated secretion of insulin and glucagon was also examined in control and CsA-treated pancreases. CsA exerted no effect on arginine-stimulated glucagon release, yet inhibited insulin approximately 50%. From these studies, we conclude that normal SRIF inhibitory mechanisms must be at least partially intact in CsA-treated pancreases during glucose-induced insulin release, and that CsA inhibition is specific for insulin release, as glucagon stores and arginine-stimulated glucagon release are unaffected by CsA.
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PMID:Inhibition by cyclosporine of insulin secretion--a beta cell-specific alteration of islet tissue function. 168 35

This study demonstrates that somatostatin (SRIF), an endogenous peptide in vestibular nuclei and cerebellum, can produce both a dose-dependent death of Purkinje cells in distinct sagittal regions of cerebellar cortex and vascular infarcts centered selectively in the inferior vestibular nucleus. Alert, adult male rats were given a 5 microliters intracerebroventricular (i.c.v.) bolus of either SRIF alone (20 or 40 micrograms) or a combined dose of SRIF plus either arginine-vasopressin (AVP, 1 micrograms) or an AVP V1 antagonist, (1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)-tyrosine)-arginine 8-vasopressin (mcAVP, 1 micrograms), through an implanted cannula. After a 4-5 day survival, the brains were stained with the cupric-silver selective degeneration method. Two types of dose-dependent lesions were observed in the cerebellar and vestibular nuclei of these animals: degeneration of Purkinje cell responses in the cerebellar cortex and vascular infarcts in vestibular nuclei. These toxic responses were unaffected by application of AVP or mcAVP; hence, they can be attributed to actions of SRIF. The distribution of Purkinje cell degeneration varied with the SRIF dose in different cerebellar regions. Purkinje cell responses in lobules I-III were equivalent at both SRIF doses, and degeneration in the copula pyramis, paraflocculus and paramedian lobule emerged at the higher SRIF dose. Purkinje cells in the medial aspect of lobules IX-X had an intermediate sensitivity to SRIF intoxication. Degenerating Purkinje cells tended to be arranged in parasagittal bands in each region, suggesting parasagittal zonal variations in susceptibility to SRIF intoxication. By contrast, infarctions in the vestibular nuclei only appeared at the higher SRIF dose. These infarcts could be unilateral or bilateral and always involved the inferior vestibular nucleus at the level of the caudal margin of the acoustic tubercle; they often extended into the medial and lateral vestibular nuclei. The infarcts had a necrotic core that was infiltrated by non-neuronal elements. Thus, they appear to reflect a direct or neurally-mediated vascular response to the peptide.
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PMID:Toxic effects of somatostatin in the cerebellum and vestibular nuclei: multiple sites of action. 168 38

The effect of helodermin (1,10,100 pmol/L), a new member of the VIP/secretin/glucagon peptide family, was investigated in glucose- (10 mmol/L) and arginine- (10 mmol/L) induced insulin, glucagon, and somatostatin secretion from the isolated perfused rat pancreas. Helodermin stimulated the somatostatin release in a concentration-dependent manner during the first (controls, 100%; 1 pmol/L, 113%, ns; 10 pmol/L, 175%, p less than 0.05; 100 pmol/L, 233%, p less than 0.05) and the second secretion phases (controls, 100%; 1 pmol/L, 117%, ns; 10 pmol/L, 210%, p less than 0.05; 100 pmol/L, 362%, p less than 0.05). There was a biphasic glucagon response with an inhibition during the first phase (controls, 100%; 1 pmol/L, 92%; 10 pmol/L, 63%, p less than 0.05; 100 pmol/L, 52%, p less than 0.05%) and a stimulation during the second phase (controls, 100%; 1 pmol/L, 117%, ns; 10 pmol/L, 210%, p less than 0.05; 100 pmol/L, 362%, p less than 0.05). Helodermin had weak stimulatory effects on pancreatic beta cells with a maximum at 10 pmol/L (first phase: controls, 100%; 1 pmol/L, 96%, ns; 10 pmol/L, 148%, p less than 0.05; 100 pmol/L, 136%, ns; second phase: controls, 100%; 1 pmol/L, 104%, ns; 10 pmol/L, 170%, p less than 0.05; 100 pmol/L, 136%, ns).
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PMID:Helodermin and islet hormone release in isolated rat pancreas. 168 42

The opioid receptor antagonist properties of four conformationally constrained cyclic octapeptide analogues of somatostatin were investigated using in vitro functional paradigms of mu-, delta- and kappa-opioid receptors in the rat brain. The analogues examined were D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP), D-Tic-CTOP (TCTOP) and D-Tic-CTAP (TCTAP). Activation of mu-receptors by the enkephalin analogue Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol (DAGO) inhibited the (electrically evoked) release of [3H]noradrenaline (NA) from superfused cortical slices and this inhibitory effect was antagonized in a competitive fashion by all of the octapeptides tested (pA2 values: CTOP and CTAP 7.9-8.0, TCTOP and TCTAP 8.7-8.8). Selective activation of kappa-opioid receptors by the cyclohexylbenzeneaceamide U69593 (0.02 microM) inhibited (by 40-45%) the release of [3H]dopamine (DA) from striatal slices, whereas selective activation of delta-opioid receptors by [D-Ser2(O-t-butyl),Leu5]enkephalyl-Thr6 (DSTBULET; 0.1 microM) caused an inhibition (by 38-46%) of striatal [14C]acetylcholine (ACh) release. However, these inhibitory effects were not affected by any of the octapeptides in concentrations that caused full antagonism of the inhibitory effect (55-65%) of 0.1 microM DAGO on cortical [3H]NA release. Thus, the cyclic octapeptide somatostatin analogues CTOP, CTAP, TCTOP and TCTAP are potent and highly selective antagonists at the mu-opioid receptors mediating presynaptic inhibition of NA release in the brain. The mu-receptor affinity of the most potent of these antagonists, TCTOP and TCTAP, appears to be similar to that of naloxone but these antagonists have a much greater selectivity than the latter.
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PMID:Cyclic somatostatin analogues as potent antagonists at mu-, but not delta- and kappa-opioid receptors mediating presynaptic inhibition of neurotransmitter release in the brain. 168 63

Somatostatins -14 and -28 are generated from a single (mammals) or two distinct (teleostean fishes) biosynthetic precursors by selective cleavage at either a dibasic (Arg-Lys) or a monobasic (Arg) site. This prohormone obviously constitutes an excellent model to study post-translational proteolytic events both at the cellular and molecular levels. Using a combination of techniques including subcellular fractionation, intracellular transport blockage and electron microscopy immunocytochemical observations, we have demonstrated unequivocally that both monobasic and dibasic proteolytic maturation occur in the Golgi apparatus of either rat brain cortex or hypothalamic cells or for somatostatin producing cells of Lophius piscatorius Brockmann organs. An arginine selective endoprotease, putative converting enzyme of prosomatostatin into somatostatin -28, has been purified and characterized from the rat intestinal mucosa.
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PMID:[Post-translational proteolytic maturation of prosomatostatin. Cellular and molecular approach]. 168 82

The effect of galanin on pancreatic hormone release was studied using isolated perifused rat pancreatic islets. In the presence of 100 mg/dl glucose, 10(-8) mol/L galanin significantly inhibited the basal somatostatin release compared with the perifusion without galanin, whereas there was no significant change in the basal insulin and glucagon release. However, under stimulation of 20 mmol/L arginine, 10(-8) mol/L galanin significantly enhanced glucagon release and suppressed insulin and somatostatin release. These effects disappeared immediately after cessation of galanin infusion. Additionally, 10(-8) mol/L galanin significantly enhanced the first and second phase of glucagon release stimulated by arginine, whereas arginine-stimulated insulin and somatostatin releases were significantly inhibited in both phases. In the cysteamine-treated rat islets, neither enhancement of glucagon release nor suppression of insulin release by galanin was reproducible. These findings indicate two possible explanations. First, it is suggested that the effects of galanin on insulin and glucagon release may be direct and reversed by non-specific effect of cycteamine. Secondly, it seems likely that galanin-enhanced glucagon release may be indirect and in part due to the concomitant somatostatin suppression. Galanin may have an important regulatory function on endocrine pancreas.
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PMID:Effect of galanin on arginine-stimulated pancreatic hormone release from isolated perifused rat islets. 168 87


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