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 first case of a tumour producing somatostatin-like immunoreactivity and bioactivity is presented. The pancreatic tumour was composed of cells indistinguishable from islet D cells. Radioimmunoassay of blood-samples obtained by tumour-vein catheterisation revealed very high levels of somatostatin immunoreactivity. On gel chromatography tumour extracts were found to contain at least 4 different immunoreactive components, one of which eluted in the position of synthetic somatostatin. Extracts from the tumour were potent in inhibiting insulin and glucagon secretion from isolated perfused porcine pancreas. Clinical abnormalities included hypochlorhydria, steatorrhoea, and diabetic glucose tolerance. Conceivably some of these abnormalities may be related to somatostatin hypersecretion from the pancreatic tumour.
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PMID:Pancreatic somatostatinoma. Clinical features and physiological implications. 6 72

To determine the effect of somatostatin on cholecystokinin-pancreozymin (C.C.K.) release, serum-C.C.K. concentrations were measured in normal volunteers after intraduodenal olive oil, with and without a simultaneous intravenous infusion of somatostatin. After instillation of the olive oil there was a rapid rise in serum-C.C.K. (integrated response 19 682+/-5632 pg min ml-1). This rise was completely abolished by somatostatin (integrated response -373+/-330 pg min ml-1, P less than 0-005) and rebound hyper-secretion was seen after the infusion had been stopped. These findings indicate that somatostatin may be involved in regulating C.C.K. release after meals, and suggest a possible explanation for the profound steatorrhoea seen in a patient with a somatostatin-producing tumour.
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PMID:Inhibition of cholecystokinin-pancreozymin release by somatostatin. 6 83

Plasma somatostatin immunoreactivity (SIR) was elevated 40-fold in an insulin-treated diabetic with disseminated pancreatic carcinoma. The diagnosis of somatostatinoma was supported by histological and ultrastructural similarities between metastatic cells and pancreatic D cells. Under acid conditions, 75% of the plasma SIR eluted as a 6000- to 7000-dalton protein and 25% as synthetic somatostatin (mol wt 1600), whereas the 20-fold elevated urine SIR consisted almost exclusively of the higher molecular weight fraction. The hypersomatostatinemia was associated with reduced basal and stimulated pancreatic hormone levels, which might reflect its involvement in the steatorrhea and diabetes, and its protection against ketoacidosis. Plasma SIR rose 50% upon insulin withdrawal and 10-fold after tolbutamide injection and fell 30% after diazoxide. It is concluded that an increase in plasma and urine SIR, the presence of a 6000- to 7000-dalton SIR fraction in plasma and urine, a reduction in basal and stimulated pancreatic hormone levels, and tolbutamide-induced somatostatin release can be diagnostic for a somatostatinoma. Streptozotocin reduced tumor volume, hypersomatostatinemia, and tolbutamide-induced somatostatin release, suggesting that this drug may be useful in the treatment of disseminated somatostatinoma.
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PMID:Plasma pancreatic hormone levels in a case of somatostatinoma: diagnostic and therapeutic implications. 15 32

Diabetes mellitus, steatorrhea, cholelithiasis and a tumor distorting the duodenum prompted a work-up for somatostatinoma in a 52-year-old man. The responses of pancreatic B-cells but not of A-cells to nutrient stimuli were inhibited, and growth-hormone release was suppressed, suggesting somatostatin resistance in some target tissues. Plasma somatostatin-like immunoreactivity ranged from 9000 to 13,000 pg per milliliter (normal: 88+/-8, mean +/- S.E.M.) and was distributed in four molecular forms, including free somatostatin. The primary tumor contained 5 microgram of somatostatin-like immunoreactivity per milligram of wet tissue, distributed in three of the molecular forms noted in plasma. Plasma calcitonin was also elevated (4650 pg per milliliter; normal: less than 120). Immunocytochemical studies showed that cells of the primary tumor contained somatostatin and calcitonin but no other peptide hormones. Only somatostatin was present in the metastases. Somatostatin was localized electron microscopically in all secretory granules, irrespective of size and shape, whereas calcitonin was present only within a single subpopulation of small granules in the same cells.
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PMID:Somatostatinoma syndrome. Biochemical, morphologic and clinical features. 37 80

The long-acting somatostatin agonist octreotide can control TSH hypersecretion from most thyrotropic adenomas. Octreotide therapy has even been shown to improve chiasmal dysfunction. We report another patient in whom octreotide therapy was associated with gradual suppression of TSH hypersecretion, which escaped partially, dramatic and very rapid and sustained improvement of chiasm compression, and dramatic and sustained shrinkage of an unresectable TSH-secreting pituitary tumour. Unusual and prolonged gastrointestinal adverse reactions eventually disappeared except for steatorrhea. In conclusion, octreotide may be considered as first line treatment in patients with unresectable thyrotropic adenomas.
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PMID:Shrinkage of a primary thyrotropin-secreting pituitary adenoma treated with the long-acting somatostatin analogue octreotide (SMS 201-995). 203 45

One of the exciting recent developments in endocrinology research has been the introduction of the somatostatin analog, octreotide into clinical practice. Octreotide provides a new therapeutic tool for diseases in which somatostatin or somatostatin-like products are secreted abnormally. Unfortunately, early experience was obtained largely with uncontrolled, compassionate drug use. When clinical information regarding octreotide is critically reviewed, evaluation is hampered by the lack of long-term studies with adequate numbers of patients and controls. Nevertheless, the information available does indicate that octreotide is promising in the acute treatment of some of the manifestations of the carcinoid syndrome, including carcinoid crisis. Similarly, octreotide ameliorates symptoms of other gut neuroendocrine tumors, particularly vasoactive intestinal peptide (VIP)-secreting tumors. Octreotide also has potential in the management of growth-hormone-secreting tumors. Long-term treatment with octreotide for these diseases requires more information regarding alterations in disease progression and development of adverse effects including variable effects on blood sugar regulation and steatorrhoea. Octreotide also has been used in nonmalignant gastrointestinal disorders, but larger studies are necessary before recommendations regarding these applications can be made. The cost of octreotide, as may be expected, is high but is justified for patients with the specific indications outlined in this review. These indications may change as understanding of the drug increases. Octreotide offers promise, particularly as acute treatment for the troublesome symptoms of several neuroendocrine disorders.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Octreotide: a long-acting somatostatin analog. 224 80

Idiopathic diarrhea is a common complication of diabetes mellitus. It occurs frequently, but not exclusively, in patients with poorly controlled insulin-dependent diabetes who also have evidence of diabetic peripheral and autonomic neuropathy. Associated steatorrhea is common and does not necessarily imply a concomitant gastrointestinal disease. The diarrhea is often intermittent; it may alternate with periods of normal bowel movements, or with constipation. It is typically painless, and occurs during the day as well as at night and may be associated with fecal incontinence. Multiple pathogenic mechanisms have been implicated, autonomic neuropathy, bacterial overgrowth, and pancreatic exocrine insufficiency being the most important underlying aberrations. However, diabetic diarrhea does not have a uniform and unequivocal pathogenesis. The diagnosis depends on a judicious clinical assessment accompanied by a stepwise laboratory evaluation, which allows the differentiation idiopathic diabetic diarrhea from the many other causes of diarrhea that can occur in diabetic and nondiabetic patients. The management can be difficult but many therapies, including antibiotics to eradicate bacterial overgrowth, as well as antidiarrheal agents, oral and topical clonidine, and somatostatin analogues may be effective in controlling diabetic diarrhea.
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PMID:Diabetic diarrhea. Pathophysiology, diagnosis, and management. 180 18

Natural somatostatin reduces plasma concentrations of many peptides, and is of short term benefit in patients with islet cell tumors, but has to be given as a continuous intravenous infusion. We review the published experience with the long acting synthetic somatostatin analogue SMS 201-995 in patients with islet cell tumors. Fifteen of 18 patients with vasoactive intestinal peptide-producing tumors, 8 of 8 patients with glucagonomas, 7 of 7 patients with unresectable insulinomas, and 3 of 3 patients with growth hormone releasing factor-producing tumors had a good sustained symptomatic response to SMS 201-995. Patients with benign insulinomas responded variably and are best treated by surgery. Patients with gastrinomas are best treated by oral gastric antisecretory agents. In all these syndromes, the clinical response to SMS 201-995 did not necessarily parallel the change in plasma concentration of marker peptide, suggesting that SMS 201-995 may have actions at various sites. The effect of SMS 201-995 on tumor size has been assessed in 46 patients, less than 20% of whom showed a reduction in tumor size. Side effects have been mild, but include steatorrhea and gastrointestinal disturbances. More studies will be required to fully assess the effects of long-term administration of SMS 201-995.
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PMID:Use of long-acting somatostatin analog SMS 201-995 in patients with pancreatic islet cell tumors. 257 86

Somatostatin (SST) has been shown to induce cholestasis in the dog and in the rat. In man, it is still unknown whether SST modifies bile formation. The present study was undertaken to examine the influence of SST on bile secretion in man. Two volunteers who had a total external biliary fistula received 1-hour SST infusions (3.5 micrograms/kg/h). Bile flow, bile acid, phospholipid and cholesterol biliary outputs were measured before, during and 1 h after the infusion. The SST infusion was associated with a pronounced decrease in bile flow and in bile acid secretion and with an increase in bile cholesterol saturation. These findings suggest that SST has cholestatic properties in man as in other species. This may provide a rational explanation for the formation of gallstones and for the steatorrhea observed in patients with somatostatinomas or during therapeutic SST administration.
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PMID:Pharmacological effect of somatostatin on bile secretion in man. 256

Octreotide is an analogue of somatostatin. Like endogenous somatostatin, it exerts a potent inhibitory effect on the release of anterior pituitary growth hormone and thyroid-stimulating hormone, and peptides of the gastroenteropancreatic endocrine system, while overcoming some of the shortcomings of exogenously administered somatostatin, namely a short duration of action, a need for intravenous administration and postinfusion rebound hypersecretion of hormone. Clinical studies have shown that octreotide is effective in the treatment of acromegaly and thyrotrophinomas. In comparative trials octreotide was significantly superior to bromocriptine in patients with acromegaly. Octreotide also appears to provide a significant advantage over existing therapies in the management of the carcinoid syndrome and offers considerable therapeutic potential in reversing carcinoid crises which may be life-threatening. Trials in patients with tumours producing vasoactive intestinal peptide demonstrated that octreotide may be an effective first-line choice for this condition, which has usually metastasised and become refractory to traditional symptomatic therapy. In limited studies in patients with high-output secretory diarrhoea, including cryptosporidium-related diarrhoea associated with AIDS and in patients with small bowel fistulas, octreotide has been shown to be effective in reducing stool/fistula output. However, well-designed clinical trials are still required to confirm its long term usefulness in these disorders. Similarly, although the use of octreotide in other conditions such as neonatal hypoglycaemia caused by nesidioblastosis, reactive pancreatitis, insulin-dependent diabetes mellitus, postprandial hypotension and the dumping syndrome has provided encouraging preliminary results, more studies are needed to clarify the place of octreotide in their treatment. Overall, octreotide appears to be well tolerated with the most frequently reported reactions being pain at the site of injection and gastrointestinal symptoms such as abdominal cramps, nausea, bloating, flatulence, diarrhoea and steatorrhoea. These adverse effects usually abate with time. Additionally, octreotide, like endogenous somatostatin, may also result in cholelithiasis, presumably by altering fat absorption and possibly by decreasing motility of the gallbladder. Thus, octreotide represents a new departure from traditional therapies in the treatment of various pathophysiological states associated with excessive peptide production and secretion. It offers a significant advantage over existing therapies in the medical management of patients with acromegaly, thyrotrophinomas, the carcinoid syndrome, tumours producing vasoactive intestinal peptide and severe secretory diarrhoea in whom conventional management options have either become exhausted or have provided suboptimal symptomatic relief.
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PMID:Octreotide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in conditions associated with excessive peptide secretion. 268 36


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