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)

Octreotide acetate (Sandostatin), a long-acting somatostatin analogue, has been demonstrated to inhibit pancreatic exocrine secretion. The effect of octreotide acetate on pancreatic endocrine function in patients undergoing pancreas surgery or pancreas transplantation has not been as well described, nor have the clinical implications been studied as systematically. This study was designed to investigate the effects of octreotide acetate on glucose metabolism and endocrine function in a partial pancreatectomized canine model, simulating reduced islet cell reserve. Serum levels of glucose, insulin, and glucagon were determined at intervals over 2 hr following an intravenous glucose tolerance test (0.5 g/kg intravenous bolus of 50% glucose) in: normal animals (Group A, n = 5), normal animals pretreated with an intravenous bolus of 400 micrograms of octreotide acetate (Group B, n = 5), partial pancreatectomized animals (Group C, n = 5), and partial pancreatectomized animals pretreated with an intravenous bolus of 400 micrograms of octreotide acetate (Group D, n = 5). Peak glucose concentration was significantly increased in Group D when compared to Group C (Group C = 304.2 +/- 13.5 mg/dl vs Group D = 353.2 +/- 12.9 mg/dl, P < 0.05), indicating an impairment of glucose metabolism by octreotide. In addition, octreotide significantly decreased peak insulin release in the partial pancreatectomy groups (Group C = 129 +/- 12.9 micro U/ml vs Group D = 47.5 +/- 6.8 micro U/ml, P < 0.05). There were no significant differences in the rate of glucose utilization or glucagon concentrations among the groups. These results demonstrate that octreotide does result in insulin suppression, with a resultant increase in stimulated glucose concentrations, in a canine model of reduced islet cell mass. Further studies are required to determine the mechanism of action of octreotide on endocrine function in the setting of pancreas transplant.
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PMID:Effect of octreotide on pancreatic endocrine function in partial pancreatectomy. 865 23

Octreotide acetate is a long-acting somatostatin analogue with protean physiologic effects. It is used primarily as an inhibitory paracrine hormone to treat a variety of medical and surgical disorders, including endocrine tumors and several gastrointestinal hypersecretory states. Because of octreotide's known inhibition of multiple trophic and anabolic hormones, we suspected that it may have deleterious effects on wound healing. Twenty-four rats were randomized to one of three groups: control, steroid (a negative control), or octreotide. Dorsal midline incisions were made and closed primarily. Wound-breaking strength measurements were performed 7 days later. The mean peak load (+/- standard error of the mean) for each group was calculated: control = 754 +/- 89 g; steroid = 378 +/- 32 g; and octreotide = 427 +/- 41 g. The difference between the control group and each of the other groups was statistically significant with P < 0.030. We conclude that octreotide has significant adverse effects on wound healing in the rat model and that these effects are comparable in magnitude to those caused by steroids.
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PMID:The adverse effects of octreotide on wound healing in rats. 912 35

Advances in medical treatment of prolactinomas and acromegaly in the last 20 years are analyzed. Dopaminergic drugs as bromocriptine, lisuride, pergolide and terguride successfully control hyperprolactinemia, reduce tumor size and cause clinical improvement. New long lasting medications with less adverse effects such as cabergoline, with oral weekly administration, and the repeatable monthly injectable form of bromocriptine (Parlodel LAR, Sandoz) may be the treatment of choice for prolactinomas. Dopaminergic medications are less effective in acromegaly. The higher doses required induce more collateral effects. An important step has been the incorporation of long lasting somatostatin analogues such as octreotide (for sbc use tid) intramuscular every 28 days injectable Sandostatin LAR and lanreotide SR (Somatuline, Ipsen Biotech), injectable every 10 to 14 days. Medical treatment of acromegaly is not, at the present, an alternative to surgery. However, the development of long lasting specific drugs may become, in the future, the choice or an alternative in the treatment of acromegaly.
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PMID:[Medical treatment of prolactin and growth hormone-secreting pituitary tumors]. 960 63

Two patients with widely metastatic papillary thyroid cancer demonstrated progressive growth of diffuse pulmonary lesions. One patient had no apparent response to high doses of 131I and the other hand no 131I uptake. 111In-pentetreotide scans revealed that many of the metastatic lesions expressed somatostatin receptors. The baseline metabolic activity and three-dimensional volume of the lesions were determined by 18F-fluoro-de-oxyglucose positron emission tomography (FDG-PET). After 3 or 4 months of octreotide (Sandostatin LAR Depot; Novartis Pharmaceutical, East Hanover, NJ) therapy, repeat FDG-PET scans revealed reductions in tumor volume and decreases in the standard uptake values of FDG. We conclude that octreotide therapy can change the biological activity of metastatic thyroid cancer lesions that exhibit somatostatin receptors.
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PMID:Inhibition of metabolic activity in papillary thyroid carcinoma by a somatostatin analogue. 1071 56

A 26-yr-old woman with type 1 diabetes and severe symptomatic autonomic neuropathy was treated with the long-acting somatostatin analogue Sandostatin LAR for intractable diarrhea. Her diarrhea had previously been successfully managed with three daily injections of octreotide without adverse consequences. She was given a single dose of Sandostatin LAR and within 2 weeks reported the development of increasingly frequent and severe headaches. Three weeks after the injection, she was admitted to hospital with severe hypertension, which eventually resolved with the administration of antihypertensive agents. No other underlying cause of the hypertension was discovered. Rechallenge of the patient with octreotide resulted in a transient hypertensive episode, which lasted 3 h. Severe hypertension, therefore, seems to be a possible adverse effect of treatment of diabetic diarrhea with somatostatin analogues, which should be used with great caution in subjects with severe autonomic dysfunction.
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PMID:Severe hypertension induced by the long-acting somatostatin analogue sandostatin LAR in a patient with diabetic autonomic neuropathy. 1072 19

Octreotide acetate is a somatostatin analogue used for the control of endocrine tumors of the gastrointestinal (GI) tract and the treatment of acromegaly. The oral absorption of octreotide is limited because of the limited permeation across the intestinal epithelium. Both chitosan hydrochloride and N-trimethyl chitosan chloride (TMC), a quaternized chitosan derivative, are nonabsorbable and nontoxic polymers that have been proven to effectively increase the permeation of hydrophilic macromolecules across mucosal epithelia by opening the tight junctions. This study investigates the intestinal absorption of octreotide when it is coadministered with the polycationic absorption enhancer TMC. Caco-2 cell monolayers were used as an in vitro intestinal epithelium model, and male Wistar rats were used for in vivo studies. Octreotide with or without polymers (TMC; chitosan hydrochloride) was administered intrajejunally in rats, and serum peptide levels were measured by radioimmunoassay. All applications and administrations were performed at neutral pH values (i.e., pH = 7.4). In vitro transport studies with Caco-2 cells revealed an increased permeation of octreotide in the presence of TMC. Enhancement ratios ranged from 34 to 121 with increasing concentrations of the polymer (0.25-1.5%, w/v). In rats, 1.0% (w/v) TMC solution significantly increased the absorption of the peptide analogue, resulting in a 5-fold increase of octreotide bioavailability compared with the controls (octreotide alone). Coadministration of 1.0% (w/v) chitosan hydrochloride did not enhance octreotide bioavailability. These results in combination with the nontoxic character of TMC suggest that this polymer is a promising excipient in the development of solid dosage forms for the peroral delivery and intestinal absorption of octreotide.
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PMID:Intestinal absorption of octreotide: N-trimethyl chitosan chloride (TMC) ameliorates the permeability and absorption properties of the somatostatin analogue in vitro and in vivo. 1086 97

Thyroid hormone inhibits thyrotropin (TSH) production and thyrotrope growth. Somatostatin has been implicated as a synergistic factor in the inhibition of thyrotrope function. We have previously shown that pharmacological doses of thyroid hormone (levothyroxine [LT4]) inhibit growth of murine TtT-97 thyrotropic tumors in association with upregulation of somatostatin receptor type 5 (sst5) mRNA and somatostatin receptor binding. In the current study, we examined the effect of physiological thyroid hormone replacement alone or in combination with the long-acting somatostatin analogue, Sandostatin LAR, on thyrotropic tumor growth, thyrotropin growth factor-beta (TSH-beta), and sst5 mRNA expression, as well as somatostatin receptor binding sites. Physiological LT4 replacement therapy resulted in tumor shrinkage in association with increased sst5 mRNA levels, reduced TSH-beta mRNA levels and enhanced somatostatin receptor binding. Sandostatin LAR alone had no effect on any parameter measured. However, Sandostatin LAR combined with LT4 synergistically inhibited TSH-beta mRNA production and reduced final tumor weights to a greater degree. In this paradigm, Sandostatin LAR required a euthyroid status to alter thyrotrope parameters. These data suggest an important interaction between the somatostatinergic system and thyroid hormone in the regulation of thyrotrope cell structure and function.
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PMID:The effect of thyroid hormone and a long-acting somatostatin analogue on TtT-97 murine thyrotropic tumors. 1095 5

Cardiovascular disease is the most severe complication of acromegaly accounting for the increased mortality of these patients. Recently, the slow-release form of octreotide (OCT; Sandostatin LAR, OCT-LAR), for im injection every 28 days, was reported to induce suppression of GH levels below 7.5 mU/L (2.5 microg/L) in 39-75% of patients, and normalization of insulin-like growth factor (IGF)-I levels for age in 64-88% of patients, with an excellent patients' compliance. The aim of the present study was to investigate the early effect of OCT-LAR treatment on the left ventricular (LV) structure and performance in 15 somatostatin analog-naive patients with acromegaly (GH, 94.8 +/- 24.9 mU/L; IGF-I, 757.9 +/- 66.6 microg/L), focusing on the early effect of GH and IGF-I suppression on the heart. Cardiac structure was investigated by echocardiography, whereas LV performance was investigated by gated-blood-pool scintigraphy, before and after 3 and 6 months of treatment with OCT-LAR. OCT-LAR was initially administered im, at a dose of 20 mg every 28 days, for 3 months. In six patients, the dose was then increased to 30 mg every 28 days to achieve disease control, which was considered when fasting and/or glucose-suppressed GH values were below 7.5 and 3.0 mU/L, respectively, together with IGF-I values within the normal range for age. The treatment with OCT-LAR for 6 months induced a significant decrease of GH (to 12.9 +/- 3.0 mU/L) and IGF-I levels (to 340.3 +/- 40.2 microg/L) in all 15 patients. After 6 months of treatment, the percent IGF-I suppression was 52.8 +/- 4.4%, and serum GH/IGF-I levels were normalized in 9 patients. A significant decrease of LV mass index (LVMi), interventricular septum thickness, and LV posterior wall thickness was observed in all 15 patients after 3 and 6 months of OCT-LAR treatment: LVMi was decreased by 19.1 +/- 2.0% without any difference in patients with (19.9 +/- 2.7%) or without disease control (17.8 +/- 3.3%). Among the 11 patients with LV hypertrophy, 6 normalized their LVMi after treatment. At study entry, an inadequate LV ejection fraction (LVEF) at rest (<50%) was found in 5 patients (33.3%), whereas an impaired response of LVEF at peak exercise (<5% increase of basal value) was found in 9 patients (60%). A significant increase in LVEF, both at rest (from 51.6 +/- 2.6 to 58.1 +/- 1.7%, P < 0.01) and at peak exercise (from 51.6 +/- 2.3 to 60.2 +/- 2.4%, P < 0.001) was found in patients with (as compared with those without) disease control (from 55.2 +/- 3.8 to 58.0 +/- 4% and from 61.8 +/- 4.6 to 61.8 +/- 3.4%, respectively). Among the 5 patients with inadequate LVEF at rest, all but 1 regained a normal LVEF after 6 months of treatment; whereas, among the 9 patients with an impaired response of the LVEF at peak exercise, 3 patients normalized, 4 improved, and 2 impaired their responses after treatment. The percent of IGF-I suppression was significantly correlated with the percent increase of resting LVEF (r = 0.644, P < 0.01). Exercise duration (from 6.0 +/- 0.7 to 7.3 +/- 0.7 min) and capacity (from 69.0 +/- 8.2 to 80 +/- 7.8 watts) were increased in the 15 patients considered as a whole, but the improvement in the exercise response was significant only in patients with disease control (P < 0.01 and P < 0.05, respectively) who also had an increase in the peak ejection rate (P = 0.03). No change in hemodynamic parameters, either at rest or at peak exercise, was found after treatment with OCT-LAR in the 15 patients. In conclusion, the results of the present study demonstrate that OCT-LAR im injections every 28 days induces a sustained suppression of GH levels and IGF-I levels in all acromegalic patients, allowing achievement of disease control in 60% of patients after 6 months of treatment. The sustained suppression of IGF-I levels was followed by a significant reduction of LVMi in all patients already after 3 months of treatment, with recovery of LV hypertrophy in 6 of 11 patients. (ABSTRACT TRUN
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PMID:Cardiovascular effects of depot long-acting somatostatin analog Sandostatin LAR in acromegaly. 1099 98

Serum leptin levels are decreased in patients with acromegaly and rise after GH is normalized by surgical treatment. We have evaluated the effect of Sandostatin LAR on leptin levels in acromegalic patients since there are recent data to suggest that somatostatin, in addition to its GH lowering effect, also reduces serum leptin levels in humans. Nineteen patients with active acromegaly were studied. Eleven patients received monthly injection of Sandostatin LAR and eight patients underwent transsphenoidal surgery. Serum concentrations of leptin, GH, IGF-1 and insulin were measured before and after treatment. Serum leptin concentrations were lower in patients with active acromegaly than controls matched for age, sex and body mass index (BMI) [2.79 microg/l (2.60) vs. 4.41 microg/l (5.07); median (inter-quartile range); P < 0.01]. A positive correlation between serum leptin concentrations and BMI was observed in the controls (r = 0.46, P < 0.05) but not in the acromegalic patients before treatment (r = 0.32, ns). In the group of patients treated with Sandostatin LAR, a marked reduction in GH and IGF-1 was achieved by week 8 and GH and IGF-1 remained suppressed throughout the 6 months of treatment. There was no change in BMI. A significant increase in leptin levels only became evident after 6 months of treatment [2.99 microg/l (2.60) vs. 4.21 microg/l (3.84), P < 0.05]. Leptin levels also significantly increased after transsphenoidal surgery [3.05 microg/l (5.73) vs. 5.19 microg/l (4.93), P < 0.05]. The positive correlation between serum leptin concentrations and BMI was restored in acromegalic patients both after treatment with Sandostatin LAR (r = 0.62, P < 0.05) and after surgery (r = 0.81, P < 0.05). Leptin concentrations were decreased in patients with active acromegaly and lowering GH by either Sandostatin LAR or transsphenoidal surgery led to an increase in leptin concentrations.
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PMID:Effect of Sandostatin LAR on serum leptin levels in patients with acromegaly. 1116 23

The primary aim of therapy should be to remove symptoms, reduce tumor bulk, prevent relapse, and improve long-term outcome. Surgery, radiotherapy and medical therapies are used to achieve these aims. Post-treatment mean "safe" serum growth hormone values of < 2.5 ng/ml should be the therapeutic goal. Transsphenoidal surgery remains the first line treatment for acromegaly. Patients with microadenoma can expect 85%, while those with macroadenoma 50% chance to achieve safe serum growth hormone levels. Less than 20% of acromegalics respond to treatment with bromocriptine, while quinagolide and cabergoline may show better clinical response; the success rate is higher for tumors secreting both growth hormone and prolactin. Dopamine agonists may be considered either in combination with somatostatin-analogues or as monotherapy in selected patients, and in those with co-secretion of prolactin. Octreotide (Sandostatin, Novartis) is a synthetic somatostatin-analogue, which is administered subcutaneously in doses between 100 and 250 micrograms 3 times daily. Long-acting octreotide (Sandostatin LAR, Novartis) contains octreotide incorporated into microspheres of biodegradable polymer. To effectively lower serum growth hormone levels, monthly injections of 10-30 mg of long-acting octreotide are needed, serum growth hormone falls to 2.5 ng/ml in 70% of cases, and serum insulin-like growth factor I normalizes in 67%. Slow release lanreotide (Somatuline SR, Ipsen) is an alternative depot long-acting somatostatin-analogue, which is administered in a dose of 30 mg intramuscularly every 14, 10 or 7 days. Both compounds are equally, if not more, effective than subcutaneous octreotide, and significantly improve patient compliance. Pegvisomant (Sensus Drug Development Corporation) is a genetically engineered growth hormone receptor antagonist, which inhibits growth hormone action. When given subcutaneously in a dose of 20 mg/day, serum insulin-like growth factor I levels return to normal in 90% of patients. Theoretical concerns of tumor expansion have not been a problem to date, but long term studies are needed. Primary medical--somatostatin-analogue--therapy is recommended if surgery fails, if the patient refuses or unsuited for surgery and it may be also considered in patients with macroadenoma with extra--but not suprasellar extension, since the surgical "cure" rates of these tumors are low.
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PMID:[Novel pharmacologic therapies in acromegaly]. 1206 60


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