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)

Continuous cell lines have been isolated from islet cell, small cell anaplastic and acinar cell carcinomas arising in the pancreas of transgenic mice, line Tg(Ela-1-SV40E)Bri18. These mice carry the pseudogene construct composed of elastase-1 promoter linked to the SV40 T antigen. Cells derived from islet cell or small cell anaplastic tumors secreted insulin and somatostatin during the early period of culture. Phenotypic alterations occurred during culture, whereby insulin secretion ceased and cells instead secreted somatostatin, indicating a change from beta-cell to delta-cell phenotype. Acinar cell lines did not secrete amylase or lipase.
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PMID:Cell lines derived from pancreatic tumors of Tg(Ela-1-SV40E)Bri18 transgenic mice express somatostatin and T antigen. 790 4

Somatostatin is a 14 amino acid peptide that inhibits pancreatic exocrine and endocrine secretion. Its clinical application has been limited by its very short half life, necessitating continuous intravenous infusion. Octreotide is an 8 amino acid synthetic analogue of somatostatin that possesses similar pharmacological effects. It has a much longer duration of action, however, and can be given subcutaneously. Both the intravenous and subcutaneous routes of injection of octreotide are well tolerated. Peak serum concentrations occur within 30 minutes after subcutaneous administration and within four minutes of a three minute intravenous infusion. Serum concentration increases linearly with dose. Octreotide is distributed rapidly, mainly in the plasma, where it is 65% protein bound. The elimination half life is about 1.5 hours and about 32% of a subcutaneous dose is excreted in the urine as unchanged octreotide. Octreotide inhibits gastroenteropancreatic secretion, especially of insulin, glucagon, pancreatic polypeptide, gastric inhibitory polypeptide, and gastrin. It also inhibits both release of thyroid stimulating hormone and growth hormone secretion in response to exercise, insulin induced hypoglycaemia, and argenine stimulation. Octreotide reduces splanchnic blood flow in healthy volunteers and hepatic venous pressure in cirrhotic patients. It can accelerate or delay gastric emptying, prolong transit time at moderate to high doses, stimulate motility at low doses, and inhibit gall bladder emptying. Octreotide considerably inhibits pentagastrin stimulated gastric acid secretion and significantly diminishes exocrine pancreatic function (amylase, trypsin, lipase). Octreotide increases intestinal transit time and decreases endogenous fluid secretion in the jejunum and ileum, thus increasing the absorption of water and electrolytes. These pharmacological effects of the analogue point to its therapeutic role in a variety of endocrine and gastrointestinal disorders.
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PMID:Somatostatin and somatostatin analogues: pharmacokinetics and pharmacodynamic effects. 791 41

The kinetics of the gastric secretion of lipase, pepsin and acid were studied after a meal in Heidenhain-pouch rabbits. After a 24-h fast, feeding immediately stimulated (< 15 min) lipase (x 4.1) and later on pepsin (x 1.8) output which reached respectively 16 and 47% of the output observed after pentagastrin stimulation (64 micrograms.kg-1.h-1 for 1 h), and which were significantly correlated. Lipase concentration was enhanced earlier and to a greater degree (x 7.3) than pepsin concentration (x 2.5). No stimulation of high basal acid secretion occurred. It was concluded that: 1) gastric lipase secretion is stimulated by feeding in the rabbit; 2) pepsin secretion is stimulated by feeding. The modalities of the secretion of lipase and pepsin are compatible with the existence of distinct secretory cells; 3) acid secretion is not stimulated by feeding. The decrease in acid secretion during the post-prandial phase favors a physiological role for lipase which is altered by low pH. The absence of acid stimulation by feeding in the rabbit, in contrast to other species, requires additional studies on the release of gastrointestinal hormones, namely gastrin, cholecystokinin and somatostatin.
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PMID:Post-prandial lipase, pepsin and acid secretion of a Heidenhain pouch in the rabbit. 821 48

Cysteamine is known to deplete somatostatin from pancreatic D cells. In the isolated perfused rat pancreas we investigated its effects on somatostatin and insulin release as well as exocrine pancreatic secretion in the presence of 16.7 mM glucose and 180 pM CCK-8. At a concentration of 0.1 mM, cysteamine had no significant effect on pancreatic endocrine and exocrine functions. At 10 mM, however, cysteamine released somatostatin (380 +/- 70 vs 100 +/- 20 fmol/20 min), inhibited insulin output (890 +/- 120 vs 13210 +/- 3260 mu units/20 min) and reduced exocrine pancreatic secretion (volume: 12 +/- 2 vs 20 +/- 2 microliters/20 min; lipase: 31 +/- 3 vs 60 +/- 7 units/20 min). We conclude that the complex changes induced by cysteamine are consistent with a physiological role of endogenous somatostatin in the regulation of insulin release. The reduction of exocrine pancreatic secretion, however, was at least in part, if not completely, mediated via the insuloacinar axis rather than a direct effect of cysteamine-released somatostatin on pancreatic acinar cells.
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PMID:Effect of cysteamine on insulin release and exocrine pancreatic secretion in vitro. 842 Jul 57

It has recently been demonstrated that the infusion of a high caloric load (3.3 kcal min-1 = 14.0 kJ min-1) into human upper jejunum inhibited pancreatic enzyme and bile salt secretion. The aim of the present study was to investigate whether this phenomenon was mediated by gastrointestinal hormones which interfere with pancreatic secretion. In six healthy volunteers, jejunal infusion of 1.3 kcal min-1 (5.5 kJ min-1) did not modify secretion of lipase and chymotrypsin to any significant extent compared with saline infusion, but the rate of 3.3 kcal min-1 (14.0 kJ min-1) resulted in an inhibition. Somatostatin and pancreatic polypeptide, which are known to inhibit exocrine pancreatic secretion, remained unchanged during jejunal nutrient infusion. The inhibition of pancreatic enzyme secretion was observed in temporal relationship with an increase of the stimulators of pancreatic exocrine secretion such as secretin, neurotensin, and CCK. The existence of an hitherto undefined inhibitor and a feedback mechanism is postulated.
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PMID:Effect of jejunal infusion of different caloric loads on pancreatic enzyme secretion and gastro-intestinal hormone response in man. 844 74

A 59-year-old man presented with painful subcutaneous nodules on the anterior surfaces of the legs. He had received oral antibiotics and supportive care for presumed cellulitis and thrombophlebitis, but had minimal improvement. Five months earlier, he had undergone pancreaticoduodenectomy for acinar pancreatic carcinoma; at that time, the serum level of amylase had been normal, but the level of lipase was elevated. The patient denied fever, rigors, arthritis/arthralgia, or pleuritic pain. His medications included aspirin, furosemide, ranitidine, and nortriptyline. He denied any allergies. Physical examination revealed numerous firm, tender, erythematous and violaceous, subcutaneous nodules on the lower extremities, with marked bilateral pitting edema (Fig. 1). Skin biopsy of a representative lesion revealed septal panniculitis, consistent with erythema nodosum (Fig. 2). None of the characteristic changes of pancreatic fat necrosis was present. The patient was treated with aspirin, 650 mg orally, q 6 h, and indomethacin, 50 mg orally, q 12 h, but he continued to develop new nodules; prednisone, 60 mg orally was begun. Although he reported improvement in symptoms, the nodules failed to respond clinically and older nodules ulcerated along the medical aspect of the right leg (Fig. 3). The complete blood count was normal, except for hemoglobin, 10.9 mg per dL. Routine serum biochemical studies were also normal, except for albumin, 3.1 mg per dL, LDH, 312 U per L, and SGOT, 51 U per L. Serum amylase was 14 U per L (normal per 30 to 115 U per L) and serum lipase was 54,160 U per L (normal 0 to 200 U per L). Chest roentgenogram and tuberculin skin test were negative. A CT scan of the abdomen revealed extensive liver metastases. A second biopsy of the skin and subcutis of a necrotic nodule revealed lobular panniculitis with the characteristic picture seen in pancreatic fat necrosis (Fig. 4). The patient was presumed to have metastatic pancreatic carcinoma and pancreatic fat necrosis. Nodules subsequently developed on the thighs, arms, hands, wrists, and fingers. He developed arthritis and arthralgias of the ankles, wrists, and hands, bilaterally, and the right knee. Aspiration of a right knee effusion revealed numerous neutrophils, but no evidence of infection. Treatment was begun with the somatostatin analog, octreotide, in increasing doses. During this therapy, the lesions did not progress and new lesions did not appear. There was no change in the lipase level. Inadvertently, octreotide was omitted at discharge, but reintroduction of octreotide was associated with lack of further progression of the nodules, according to the patient's spouse; however the patient became progressively debilitated and his abdominal pain worsened, requiring continuous sedation. His condition deteriorated and he died several weeks after hospital discharge.
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PMID:Fat necrosis with features of erythema nodosum in a patient with metastatic pancreatic carcinoma. 883 28

Somatostatin is a potent inhibitor of endocrine and exocrine pancreatic secretion. However, it is not clear whether it also inhibits pancreatic growth. Therefore we treated male Wistar rats with a somatostatin analogue, octreotide (12-192 micrograms/(kg body wt.day)), over a period of 14 days. In a dose-dependent manner, this potent and long-acting analogue caused a reduction in weight of the pancreas and a reduction in pancreatic content of protein, DNA, trypsin, chymotrypsin, amylase and lipase, as well as pancreatic content of insulin-, glucagon- and somatostatin-like immunoreactivities. When growth of rat pancreas was induced by oral administration of camostate (200 mg/(kg body wt. day) or by subcutaneous administration of cholecystokinin (2 x 10 micrograms/(kg body wt. day)) over a period of 14 days, octreotide (12-192 micrograms/(kg body wt.day)) had the same effects, but these were even more pronounced. We conclude that somatostatin is an important regulator of pancreatic growth.
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PMID:Rat pancreas after long-term treatment with the somatostatin analogue octreotide. 896 3

We demonstrated previously that pancreatic secretion of individual enzymes is specifically regulated (1). In the present study, we investigated and defined contributing roles of cholinergic and cholecystokinin tones to the specific regulation of rat pancreatic secretion of digestive enzymes. Animals were provided with pancreatic, biliary, duodenal, and jugular vein cannulas allowing separate drainage of bile and pure pancreatic juice, as well as intravenous infusions of MK329 or atropine sulfate along with SMS 201-995 (SMS). Rats kept in restraint cages were divided into four groups. The first rat group was infused with 5 micrograms kg-1 h-1 SMS alone; the second group was infused with a mixture of SMS and MK329 (5 micrograms kg-1 h-1:0.5 mg kg-1 h-1); the third group received a mixture of SMS and atropine (5 micrograms kg-1 h-1); and rats in the fourth group were administrated a mixture of SMS, MK329, and atropine (5 micrograms kg-1 h-1:0.5 mg kg-1:100 micrograms kg-1 h-1). Food, but not water, was denied rats 10 h before the experiment and throughout the 6-h experimental period. During the experiment, pancreatic juice was continuously collected every 15 min from each rat, and a 15-microliter aliquot of the pancreatic juice sample was removed for total protein, amylase, lipase, trypsinogen, chymotrypsinogen, and proelastase assays. Pancreatic juice previously collected from a donor rat was mixed with the fresh bile and the mixture was recirculated into the duodenum. The secretory patterns over the 6-h experimental period showed that during the first hour of drug infusion, MK329 alone did not alter the SMS-induced inhibitory process of total protein and amylase, trypsinogen, and proelastase secretion, and there was no marked change in total protein and enzyme outputs. Adding atropine to SMS did not alter the secretory pattern during the first hour of drug infusion, but a significantly greater decrease in protein and enzymes outputs occurred. Correlations between paired enzyme outputs greatly increased with SMS alone, but some changed when either MK329 or atropine was infused along with SMS. When all drugs were infused together, enzyme outputs became strongly correlated. These results suggest that under fasting conditions, somatostatin and atropine can neutralize basal pancreatic enzyme outputs, leading to a constitutive type of secretion characterized by parallel secretion of the digestive enzymes. Furthermore, it is proposed that under basal secretion conditions, acetylcholine and cholecystokinin reaching the pancreatic acinar cells may act to dissociate pancreatic secretion of individual digestive enzymes originating from heterogeneous secretory granules.
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PMID:Modulation of pancreatic secretion of individual digestive enzymes in octreotide (SMS 201-995)-infused rats. 898 7

The aims of medical therapy in chronic pancreatitis are mainly to relieve the recurrent pain and to correct any malabsorption secondary to digestive insufficiency resulting from deficient exocrine pancreatic function. The treatment of the pain initially involves the use of dietary measures and analgesic drugs. The results of the use of pancreatic extracts and somatostatin reported in the literature are controversial, as are those of coeliac plexus block. Of unquestionable efficacy, at least in the short to medium term, are surgical decompression interventions in patients, with pain refractory to these measures and who present significant dilation of Wirsung's duct at ERCP. Endoscopic decompression constitutes an alternative to surgical decompression. In view of the transitory results of endoscopic decompression, which, in any event, should be implemented only by endoscopists possessing the necessary experience and expertise, the use of this technique may perhaps be targeted at carefully selected patients to be submitted to surgical decompression. As far as maldigestion is concerned, which occurs only when the pancreatic functional deficit reaches 90% or more, replacement therapy with pancreatic extracts must be resorted to. Multi-Unit Dose preparations are to be preferred, consisting in gastro-protected microspheres measuring not more than 2 mm in diameter and containing high doses of lipase, since at least 30,000 I.U. of lipase are required in the post-prandial phase for reasonably satisfactory correction of the steatorrhoea. Should this fail to prove effective, it is good policy to add antisecretory drugs (H2-antagonists, proton-pump inhibitors).
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PMID:[The medical therapy of chronic pancreatitis. Problems, progress and outlook]. 902 57

Bile salts are intraduodenal stimulants of basal pancreatic secretion. This study aims to show whether the three main bile salts of human bile differ in their action on pancreatic secretion, and whether they enhance or inhibit each other after combined use. Furthermore, the effect on gastroenteropancreatic peptide release is evaluated. Twelve subjects were provided with a gastroduodenal double-lumen tube. Equimolar doses (0.6 mmol) of taurocholate (322 mg), taurodeoxycholate (313 mg), and a combination of both stimuli were given intraduodenally. Another 12 subjects received taurochenodeoxycholate (313 mg) instead of taurocholate. Volume, bicarbonate, trypsin, and lipase were determined in duodenal aspirates. Cholecystokinin, pancreatic polypeptide, and somatostatin were measured radioimmunologically in plasma samples. All bile salts and combinations exerted a significant hydrokinetic and ecbolic effect. The hydrokinetic response of the combined stimuli was significantly higher as compared with taurocholate and taurochenodeoxycholate, respectively. As far as concerns the ecbolic response, the difference was significant only for trypsin output as compared with taurochenodeoxycholate. Plasma cholecystokinin rose significantly only after the combined stimuli. Pancreatic polypeptide and somatostatin increased significantly after all stimuli, except pancreatic polypeptide after taurocholate. Combined use enhances the hydrokinetic and ecbolic effects of single bile salts. Cholecystokinin may, hereby, be involved as a mediator of the ecbolic effect. Pancreatic polypeptide release indicates cholinergic mechanisms as further mediators. As demonstrated by somatostatin release, counter-regulatory mechanisms are also triggered by intraduodenal bile salts.
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PMID:Exocrine pancreatic secretion and plasma levels of cholecystokinin, pancreatic polypeptide, and somatostatin after single and combined intraduodenal application of different bile salts in man. 903 83


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