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)

Proliferative retinopathies account for the majority of cases of vision loss throughout the world. Currently accepted therapy for retinopathy consists of retinal ablation by panretinal laser photocoagulation or cryotherapy. This technique is not without deleterious effects to patients, including diminished night vision, reduced peripheral vision and loss of precise vision, decreasing visual acuity by one to two lines in magnitude. One promising area of research into pharmacotherapeutics for retinopathies, especially proliferative diabetic retinopathy, involves the use of synthetic analogues of somatostatin. The rationale for somatostatin as a therapeutic agent for retinal neovascularization is discussed. Somatostatin analogues such as octreotide have shown promise as a safe and effective treatment for severe proliferative diabetic retinopathy by blocking the local and systemic production of growth hormone and insulin-like growth factor type 1 associated with angiogenesis and endothelial cell proliferation. There are also observations suggesting an autocrine and paracrine effect of somatostatin, perhaps directly on retinal cells, which are known to express somatostatin receptors (SSTR). SSTR2 and SSTR3 are the most important receptor subtypes mediating growth hormone secretion and endothelial cell cycle arrest, retinal endothelial cell apoptosis and release of insulin. Thus, analogues that target these receptor subtypes may prove more useful. Long-acting somatostatin analogues are currently being tested for treatment of diabetic retinopathy and are, in fact, the only therapeutic alternative for patients who fail panretinal photocoagulation. Whether such a therapy may also prove effective for other retinal vascular proliferative diseases such as retinopathy of prematurity and age-related macular degeneration remains an open question that deserves attention, given our new understanding of the cellular and molecular mechanisms by which somatostatin may exert its antiangiogenic effects.
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PMID:Somatostatin analogues as drug therapies for retinopathies. 1258 62

Somatostatin analogues are potent growth hormone and glucagon inhibitors and are commonly used in the treatment of several endocrine and non-endocrine disorders. We report severe and longstanding hypoglycemia triggered by long-acting octreotide (Sandostatin LAR) in a 62-year-old women with malignant mesenchymal tumor. Hypoglycemia developed after 6 hours of octreotide injection and she was admitted to the emergency unit with sweating, tremor, palpitation and confusion. On admission, her plasma glucose level was: 17 mg/dl (normal: 65-110), cortisol: 31 microg/dl (normal: 5-25), insulin: 4.32 microIU/ml (normal: 6-27), C-peptide: 2.64 ng/ml (normal: 0.9-4.0), growth hormone: 0.06 ng/ml (normal: 0.06-5.0), insulin-like growth factor-I: 8.5 ng/ml (normal: 101-303), insulin-like growth factor binding protein-3: 1715 ng/ml (normal: 2020-3990). Intravenous dextrose infusion was given for a month to sustain normoglycemia since hypoglycemia recurred following cessation of infusion. Therefore, prednisolone, 35 mg/day was added and the parenteral dextrose infusion rate was decreased gradually and finally stopped. Normoglycemia could be maintained with prednisolone 20 mg/day. In patients prone to tumor hypoglycemia, long-acting octreotide may trigger severe and prolonged hypoglycemia due to suppression of counter-regulatory hormones; clinical trial with short-acting octreotide may be warranted to predict and prevent this life-threating complication.
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PMID:Severe and prolonged hypoglycemia triggered by long-acting octreotide in a patient with malignant mesenchymal tumor: case report. 1267 21

Although acromegaly remains a disease primarily addressed by pituitary microsurgery, most patients require secondary treatment for persistent growth hormone (GH) hypersecretion and elevated serum insulin-like growth factor-1 (IGF-1) concentrations following adenomectomy. Persistently abnormal serum GH and IGF-1 can be reduced to normal concentrations in better than half of post-surgery acromegalics using the pharmacologic treatments available at present, the dopamine agonists (DA) and somatostatin (SST) analogs. The long-acting SST analogs octreotide LAR and lanreotide SR have become the mainstay of medical treatment for acromegaly, having largely supplanted DA agents since the introduction of bromocriptine for the suppression of GH secretion in the 1970s. The DA cabergoline may be effective in up to half of patients, however, in particular those patients whose tumors cosecrete prolactin. On the horizon is the GH-receptor antagonist pegvisomant, which is expected to enable the reduction of serum IGF-1 to the normal range in the vast majority of postoperative acromegaly patients, representing a revolutionary development in the medical treatment of this disease. We here review the choices available to the endocrinologist in the pharmacologic treatment of acromegaly, focusing upon the SST analogs.
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PMID:Somatostatin analogs in medical treatment of acromegaly. 1272 7

A rational drug design approach, capitalizing on structure-activity relationships and involving transposition of functional groups from somatotropin release inhibitory factor (SRIF) into a reduced size cyclohexapeptide template, has led to the discovery of SOM230 (25), a novel, stable cyclohexapeptide somatostatin mimic that exhibits unique high-affinity binding to human somatostatin receptors (subtypes sst1-sst5). SOM230 has potent, long-lasting inhibitory effects on growth hormone and insulin-like growth factor-1 release and is a promising development candidate currently under evaluation in phase I clinical trials.
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PMID:A novel somatostatin mimic with broad somatotropin release inhibitory factor receptor binding and superior therapeutic potential. 1277 38

Severe thyroid associated dermopathy (TAD), a rare complication of Graves' disease, currently lacks effective treatment. Mediators of growth and inflammation, including insulin-like growth factor-1 (IGF-1) and somatostatin (SST) have been implicated in its pathogenesis. Octreotide, a potent SST analogue, has been used in TAD with anecdotal success. Therefore, we evaluated the efficacy of long-term octreotide therapy in moderate to severe TAD. Three obese women with TAD were studied. Baseline treatment included levothyroxine, methimazole, fluocinonide ointment under occlusive dressing, and physiotherapy for lymphedema. After establishing baseline clinical status, octreotide was started (300 microg subcutaneously daily) for 10 to 28 months. Studies obtained at baseline and every 3 months included: leg circumference, skin examination, clinical photography, self-reported clinical status, body mass index (BMI), serum thyrotropin (TSH) and free thyroxine, titers of antithyroidal and anti-TSH receptor antibodies. Minimal changes in the edema, erythema, skin texture and size of nodules were observed. The minor changes seen followed significant decreases in the patients' BMI, and hence, cannot be specifically attributed to octreotide administration. No clinically significant benefit from long-term octreotide therapy was demonstrated in three patients with moderate to severe TAD. Weight loss and measures such as compression bandaging and topical corticosteroid application still remain the most cost effective treatment modalities for TAD.
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PMID:Lack of effect of long-term octreotide therapy in severe thyroid-associated dermopathy. 1285 13

Octreotide long-acting release (LAR) is a somatostatin analogue designed for once monthly intramuscular injection. As with endogenous somatostatin, octreotide LAR inhibits secretion of growth hormone (GH) as well as various other peptide hormones. In the treatment of acromegaly, octreotide LAR effectively controlled the secretion of GH and insulin-like growth factor-1 (IGF-1) in about 55-70% of patients (n > 100) who had previously been treated with somatostatin analogues, a similar degree of control to that observed with subcutaneous octreotide and lanreotide slow release (SR). Progressive control of serum levels of GH and IGF-1 was achieved with octreotide LAR in clinical studies of up to 4 years' duration. In addition, primary therapy with octreotide LAR provided effective control of GH and IGF-1 secretion, particularly in patients with a pretreatment GH level <20 microg/L. The percentage of patients achieving a target serum GH level of <2-2.5 micro g/L or normal IGF-1 levels was significantly greater with octreotide LAR 10, 20 or 30 mg every 28 days than with lanreotide SR 30 mg every 7-14 days in a large (n = 125) sequential, 6-month study, but was not significantly different between treatment groups in a small, randomised, nonblind, parallel group study of previously untreated patients. The volume of pituitary tumour shrinkage achieved with octreotide LAR or lanreotide SR was also similar ( approximate, equals 33% after 24 months). Acromegaly symptoms, such as headache, increased perspiration, paraesthesia, fatigue and osteoarthralgia were improved during treatment with octreotide LAR or lanreotide SR. Overall, octreotide LAR is generally well tolerated by most patients. The incidence of gastrointestinal symptoms is about 30% but, in most cases, events are transient and mild to moderate. Gallbladder abnormalities (sediment, sludge, microlithiasis and gallstones) can occur, but only 1% have become symptomatic to date. The prevalence of biliary abnormalities did not change after switching from subcutaneous octreotide, or from lanreotide SR, to octreotide LAR. Glucose metabolism can be affected by octreotide LAR in some patients; about 15% become hyperglycaemic, usually mild in severity. In summary, octreotide LAR controls GH and IGF-1 secretion in about 55-70% of patients with acromegaly. Octreotide LAR is administered intramuscularly every 28 days, offering improved patient compliance and convenience over three-times-daily subcutaneous octreotide. Long-term therapy provides progressive control of serum GH and IGF-1 levels, and is generally well tolerated by most patients. Thus, for the medical management of acromegaly, octreotide LAR is an effective, well tolerated and convenient treatment option.
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PMID:Octreotide long-acting release (LAR): a review of its use in the management of acromegaly. 1460 59

Pituitary adenomas are mostly benign tumours that originate from differentiated anterior pituitary cells. Altered expression of growth factors or their receptors could enhance clonal expansion of pituitary adenoma cells. GHRH overstimulation or an activating point mutation in the Gs a-subunit leads to increased GH secretion and tumour formation. In contrast, IGF-I suppresses basal and GHRH-stimulated GH secretion in pituitary adenoma cells, whereas prolactin secretion is unaffected. Somatostatin analogues and pegvisomant, a novel growth hormone-receptor antagonist, results in a reduction of serum IGF-I levels and clinical improvement in patients suffering from pituitary adenoma. Thus, this review focuses on the role of the growth hormone/insulin-like growth factor system in pituitary tumorigenesis with particular focus on the genetic alterations described in pituitary adenomas up to now.
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PMID:The role of the GH/IGF system in pituitary tumorigenesis. 1471 Mar 44

Basal serum growth hormone, insulin-like growth factor-1 (IGF-1) and somatostatin concentration were measured by standard radioimmunoassay in patients with a diagnosis of rheumatoid arthritis (RA) according to the criteria of the American College of Rheumatology as well as in a group of age-matched normal subjects. RA patients exhibited significantly elevated (age, 45-55 yrs, p less than 0.05; 55 yrs and older, p less than 0.01) serum growth hormone levels compared to age-matched individuals from the control group. IGF-1 was unchanged. Serum somatostatin levels were reduced in RA patients between 45 and 55 yrs but reached a significant reduction (p less than 0.0001) in RA patients, 55 years and older compared to age-matched individuals from the control group. RA patients treated with prednisone did not exhibit changes in either growth hormone or IGF-1 levels compared to RA patients treated principally with non-steroidal anti-inflammatory drugs and methotrexate. These results indicated that symptomatic RA is associated with elevated serum growth hormone without concomitant changes in IGF-1 compared to individuals from the control group. Reduced somatostatin levels in older RA patients resulted in a skewed upward growth hormone to somatostatin ratio. We conclude that the serum growth hormone to somatostatin ratio may be a useful surrogate marker of disease activity in symptomatic RA.
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PMID:The serum growth hormone to somatostatin ratio is skewed upward in rheumatoid arthritis patients. 1497 77

We previously characterized three cDNAs obtained from the endocrine pancreas (Brockmann body) of rainbow trout that encode for distinct preprosomatostatin (PPSS) molecules: PPSS I containing somatostain-14 (SS-14) at its C-terminus and two separate PPSS IIs, PPSS II' and PPSS II'', containing [Tyr7,Gly10]-SS-14 at their C-termini. In this study, we examined the control of PPSS I, PPSS II', and PPSS II'' mRNA expression by growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Rainbow trout implanted with GH for 21 days displayed elevated pancreatic expression of all PPSS mRNAs compared to control animals. Growth hormone directly stimulated the expression of all pancreatic PPSS mRNAs in vitro in a dose-dependent manner; however, GH was a more potent stimulator of PPSS II' expression than of PPSS I or PPSS II'' expression. Insulin-like growth factor-1 also directly stimulated the expression of PPSS mRNAs in a dose-dependent manner in Brockmann bodies incubated in vitro; IGF-1 was a more potent stimulator of PPSS I and PPSS II' expression than of PPSS II'' expression. These results indicate that the expression of PPSS mRNAs in the Brockmann body of trout is differentially regulated by GH and IGF-1 and suggest that SS mediate the feedback regulation of GH and IGF-1.
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PMID:Growth hormone and insulin-like growth factor-1 differentially stimulate the expression of preprosomatostatin mRNAs in the Brockmann bodies of rainbow trout, Oncorhynchus mykiss. 1508 35

Cancers of the stomach, colon and exocrine pancreas are major international health problems and result in more than a million deaths worldwide each year. The therapies for these malignancies must be improved. The effects of gastrointestinal (GI) hormonal peptides and endogenous growth factors on these cancers were reviewed. Some GI peptides, including gastrin and gastrin-releasing peptide (GRP) (mammalian bombesin), appear to be involved in the growth of neoplasms of the GI tract. Certain growth factors such as insulin-like growth factor (IGF)-I, IGF-II and epidermal growth factor and their receptors that regulate cell proliferation are also implicated in the development and progression of GI cancers. Experimental investigations on gastric, colorectal and pancreatic cancers with analogs of somatostatin, antagonists of bombesin/GRP, antagonists of growth hormone-releasing hormone as well as cytotoxic peptides that can be targeted to peptide receptors on tumors were summarized. Clinical trials on peptide analogs in patients with gastric, colorectal and pancreatic cancers were reviewed and analyzed. It may be possible to develop new approaches to hormonal therapy of GI malignancies based on various peptide analogs.
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PMID:New approaches to therapy of cancers of the stomach, colon and pancreas based on peptide analogs. 1511 52


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