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)

To investigate how blindness influences GH secretion, we studied the GH response to L-dopa and arginine in 8 blind adult males and 10 normal age-matched control males. Arginine and L-dopa tests were performed in random order at least 1 week apart at 0800 h, and plasma GH was measured by RIA. The blind subjects showed GH responses to arginine similar to those in normal subjects [peak, 22.1 +/- 1.3 vs. 20.5 +/- 1.3 micrograms/L (+/- SE)], but their GH response to L-dopa was significantly reduced [peak, 5.4 +/- 1.3 vs. 20.3 +/- 2.4 micrograms/L (+/- SE); P less than 0.01]. Because L-dopa is believed to release GH by stimulating endogenous GHRH, whereas arginine may act by suppressing endogenous somatostatin secretion, we propose that blindness may impair GH release by inhibiting GHRH secretion.
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PMID:Blindness impairs plasma growth hormone response to L-dopa but not to arginine. 231 45

Glucagon, somatostatin and insulin secretions were evaluated in a new type of perfusion preparation: the naturally A and D cell rich splenic bulb of duck pancreas. Stable basal levels were observed with 11 mM glucose, corresponding to normoglycaemia, and all secretions were stimulated by 1 mM 3-isobutyl-1-methyl-xanthine and by 10 mM arginine, demonstrating the technique's validity. In the absence of aminoacids in the perfusion medium, A cell blindness to glucose was corrected by physiological levels of insulin (2 ng/ml); insulinodependency of A cells, and unresponsiveness of D cells to glucose, probably not ruled by insulin, were observed. However, in the presence of aminoacids, glucagon was inhibited and somatostatin secretion stimulated by glucose (33 mM), independently of insulin (2 ng/ml). Aminoacids greatly influenced pancreatic hormone release.
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PMID:Glucagon and somatostatin secretion from the perfused splenic bulb of duck pancreas. 243 Apr 19

After mentioning insulin deficiency diabetes in animals produced by drugs such as Alloxan, Diazoxide or Streptozotocin only drugs are discussed, which are used in elderly patients and may either provoke diabetes mellitus (or temporary hyperglycemia) or may change the clinical course of diabetes. In the first group endocrine products such as corticosteroids, estrogens, somatotrophic hormone, thyroid hormone, glucagon, somatostatin, catecholamines and hormones with anabolic effects are listed. The second group comprises saluretics, salicylates, amphetamines, pentamidine, nicotinic acid and its derivatives, beta-receptor blockers and finally laxatives. Hypopotassemia alone can also be the cause of hyperglycemia. Speaking of the sulfonylureapreparations, their interaction with alcohol, with phenylbutazone, with some sulfonamides and the effect of the sulfonylureas on peripheric insulin-receptors is discussed. In case of severe diabetic vascular disease the use of anticoagulants may lead to hemorrhages. If such an hemorrhage occurs in the eyes, it may lead to blindness. In diabetic nephropathy the use of phenacetine and its derivatives should be substituted by another medication. This review is not at all complete but should only show some of the problems in the treatment of elderly diabetic patients.
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PMID:[Iatrogenic diabetes mellitus (side effects and interactions of drugs during clinical diabetes mellitus (author's transl)]. 612 38

In the present study, facial skin from so-called "screen dermatitis" patients were compared with corresponding material from normal healthy volunteers. The aim of the study was to evaluate possible markers to be used for future double-blind or blind provocation investigations. Differences were found for the biological markers calcitonin gene-related peptide (CGRP), somatostatin (SOM), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine amide (PHI), neuropeptide tyrosine (NPY), protein S-100 (S-100), neuron-specific enolase (NSE), protein gene product (PGP) 9.5 and phenylethanolamine N-methyltransferase (PNMT). The overall impression in the blind-coded material was such that it turned out easy to blindly separate the two groups from each other. However, no single marker was 100% able to pin-point the difference, although some were quite powerful in doing so (CGRP, SOM, S-100). However, it has to be pointed out that we cannot, based upon the present results, draw any definitive conclusions about the cause of the changes observed. Whether this is due to electric or magnetic fields, a surrounding airborne chemical, humidity, heating, stress factors, or something else, still remains an open question. Blind or double-blind provocations in a controlled environment are necessary to elucidate possible underlying causes for the changes reported in this investigation.
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PMID:A screening of skin changes, with special emphasis on neurochemical marker antibody evaluation, in patients claiming to suffer from "screen dermatitis" as compared to normal healthy controls. 898 Oct 27

In this review we describe some of the remarkable and intricate mechanisms through which the calcium ion (Ca2+) contributes to detection, transduction and synaptic transfer of light stimuli in rod and cone photoreceptors. The function of Ca2+ is highly compartmentalized. In the outer segment, Ca2+ controls photoreceptor light adaptation by independently adjusting the gain of phototransduction at several stages in the transduction chain. In the inner segment and synaptic terminal, Ca2+ regulates cells' metabolism, glutamate release, cytoskeletal dynamics, gene expression and cell death. We discuss the mechanisms of Ca2+ entry, buffering, sequestration, release from internal stores and Ca2+ extrusion from both outer and inner segments, showing that these two compartments have little in common with respect to Ca2+ homeostasis. We also investigate the various roles played by Ca2+ as an integrator of intracellular signaling pathways, and emphasize the central role played by Ca2+ as a second messenger in neuromodulation of photoreceptor signaling by extracellular ligands such as dopamine, adenosine and somatostatin. Finally, we review the intimate link between dysfunction in photoreceptor Ca2+ homeostasis and pathologies leading to retinal dysfunction and blindness.
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PMID:Calcium regulation in photoreceptors. 1216 44

Ocular diseases such as proliferative diabetic retinopathy are the major cause of blindness in industrialized countries. The main pathologic features of these diseases are hypoxia and overproduction of growth factors resulting in pathologic proliferation of endothelial cells and new vessel formation. Particularly, hypoxia and growth factors, such as VEGF, IGF-1, bFGF and TGF beta(2), show a complex interaction in the onset and progression of the diseases. Therefore, to date, most therapeutic strategies for proliferative retinopathies have targeted proliferation of endothelial cells evoked by growth factors. Recently, a synthetic analog of somatostatin, octreotide, has been shown to inhibit the proliferation of various cells in vitro, including endothelial cells. In this study, we have investigated the proliferative response of bovine retinal endothelial cells (BREC) to growth factors under hypoxic conditions and the modulation by octreotide. We found a dose-dependent increase of cell proliferation with VEGF, IGF-1 and bFGF, and inhibition of hypoxia-induced cell proliferation with TGF beta(2). Moreover, growth factor-induced, but not hypoxia-induced, cell proliferation was attenuated in the presence of octreotide. In contrast, TGF beta(2) abolished hypoxia-induced BREC proliferation. Similar to octreotide BIM23027, a somatastatin receptor subtype 2 (SSTR2) receptor agonist was able to attenuate the growth factor-induced proliferation of BREC expressing mRNA and protein for SSTR2. Therefore, we postulate that octreotide exerts its effects mainly through binding to the SSTR2. Taken together, our findings point to octreotide as a promising candidate for the treatment of eye disorders involving growth factor-dependent proliferation of endothelial cells.
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PMID:Octreotide prevents growth factor-induced proliferation of bovine retinal endothelial cells under hypoxia. 1501 96

The role of somatostatin and growth hormone in eye diseases recently became a matter of interest because of its link with proliferative diabetic retinopathy. In diabetic patients the pathologic proliferation of blood vessels as a result of retinal ischemia is a major cause of blindness. The hypoxic portions of the retina release angiogenic factors, stimulating neovascularization. Somatostatin is a natural peptide hormone that affects the release of a number of other hormones, such as growth hormone, glucagon, insulin and gastrin. The somatostatin analog promises to be safe and effective treatment for severe diabetic retinopathy. This compound has been shown to block the local and systemic production of insulin-like growth factor 1 and growth hormone, which promote the angiogenesis and endothelial cell proliferation associated with proliferative retinopathy. Several studies have confirmed that using somatostatin analogs to block insulin-like growth factor 1 production is effective in reducing neovascularization and preventing disease progression to proliferative stage of diabetic retinopathy. Long-acting somatostatin analogs are currently being tested for the treatment of diabetic retinopathy. The development of somatostatin analogs with increased selectivity for receptor subtypes will provide improved outcomes in the management of patients with diabetic retinopathy.
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PMID:Diabetes mellitus and retinopathy. 1507 18

Neovascularization stimulated by IGF-1 mediated induction of vascular endothelial growth factor (VEGF) is one of the leading causes of blindness in humans. It plays a central role in the pathogenesis of proliferative diabetic retinopathy (DR), neovascular glaucoma, exudative age-related macular degeneration (AMD) and retinopathy of prematurity. Neovascularization is a multi-step process that involves complex interactions of a variety of mitogenic factors such as VEGF and IGF-I which are produced locally in the human eye by a variety of cells including retinal pigment epithelial (RPE) cells, retinal capillary pericytes, endothelial cells, Mueller cells and ganglion cells. We hypothesized that somatostatin would inhibit the IGF-1 signal transduction pathway in RPE cells, resulting in decreased VEGF production. We have observed expression of somatostatin receptor protein in retinal pigment epithelial (RPE) cells of the human eye using immunohistochemistry and have confirmed expression of somatostatin receptors in cultured human RPE cells using reverse transcriptase-PCR. IGF-1 induced a dose dependent increase in IGF-1R phosphorylation and in VEGF mRNA levels in cultured human RPE cells. Somatostatin and octreotide, a somatostatin analogue, inhibited IGF-1 receptor (IGF-1R) phosphorylation and decreased VEGF production. Both IGF-1R phosphorylation and accumulation of VEGF mRNA were inhibited by physiological levels of somatostatin and octreotide (1 nM). These results demonstrate somatostatin and octreotide mediated attenuation of both IGF-1R signal transduction and VEGF mRNA accumulation via somatostatin receptor type 2 (sst2). Furthermore, these data suggest a rationale for the use of octreotide as a prophylactic and therapeutic option in disease states that cause ocular neovascularization.
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PMID:Somatostatin inhibits IGF-1 mediated induction of VEGF in human retinal pigment epithelial cells. 1538 Oct 31

Angiogenic eye disease is among the most common causes of blindness worldwide. Current treatment approaches are insufficiently effective and partially associated with significant adverse effects. From an investigational view, the eye provides an ideal setting to observe real-time and serial observations of angiogenesis in vivo in humans. The current understanding of molecular biology involved in angiogenesis has already led to the identification of a number of potential therapeutic targets, some of them being highly effective angiostatic molecules. Most experimental approaches currently favour or even require the systemic administration of the investigated substances (somatostatin analogues, PKC-inhibitors). However, the systemic administration of bioactive substances always risks significant systemic adverse effects. Due to the morphological characteristics of the eye, local therapies including intraocular injection or even local gene transfer might be feasible. They might provide a valuable opportunity of targeted and sustained delivery of therapeutic proteins to the retina. This review aims to outline the current understanding of the pathogenesis of proliferative diabetic retinopathy and will focus on some as yet experimental, but potentially effective new therapeutic possibilities of this disease.
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PMID:Novel approaches in the treatment of angiogenic eye disease. 1602 67

Worldwide, ocular cataracts are a major cause of human blindness. A key goal of cataract-related research is to identify simple, cost-efficient but effective ways to prevent cataract formation or progression. Genistein is a naturally occurring dietary isoflavone with well-documented estrogenic, antioxidant, and protein tyrosine kinase inhibitor activity, which in turn modulates the activity of several enzymes involved in cell signaling and proliferation. Furthermore, many isoflavones have been shown to be potent inhibitors of aldose reductase, which is an important rate-limiting enzyme in the process of cataract induction in the metabolic disease galactosemia. In order to assess the potential for genistein to mitigate cataract formation, we have studied its effects in the animal model of dietary galactose-induced cataracts in adult male rats. Our experimental hypothesis was that dietary genistein would prevent or delay the progression of cataracts induced by high dietary intake of galactose. Our results show that the isoflavone genistein was not able to completely prevent galactose-induced cataract formation, but genistein did delay the progression of cataracts induced by dietary galactose. In addition, we found that dietary galactose decreased concentrations of serum somatostatin, while adding genistein decreased the serum glucose level but increased the serum testosterone level. As an initial inquiry into the mechanisms by which the partial protective effect of genistein could be mediated, we found that genistein increased the expression of connexin (Cx) 43 in the lens but did not affect the expression of soluble guanylyl cyclase (sGC) subunits. This finding suggests that the partial protective effect of genistein on cataract induction appears to be unrelated to sGC but may be mediated by enhanced expression of Cx43 and changed metabolic state.
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PMID:Effect of the isoflavone genistein against galactose-induced cataracts in rats. 1720 92


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