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 (SMS 201-995) is a long-acting somatostatin analogue that inhibits exocrine pancreatic secretion and that has been proposed for treatment of various pancreatic disorders. To gain more information about the mechanism by which octreotide inhibits pancreatic enzyme secretion, we studied the effect of this compound on plasma amino acid uptake by the pancreas in six healthy volunteers aged 22-29 years. Pancreatic amino acid uptake was assessed by measuring plasma amino acid concentration before and during pancreatic enzyme synthesis stimulation with cerulein (50 ng/kg/h). The infusion of cerulein caused a significant decrease (p less than 0.001) in plasma amino acid concentration. The subcutaneous injection of octreotide at dosages of 12.5, 25, and 50 micrograms prevented this decrease in a dose-dependent manner. The decrease in amino acid concentration reached a maximum of 19.4 +/- 2.4% during cerulein infusion and a maximum of 10.7 +/- 2.5, 6.8 +/- 1.2, and 2.9 +/- 1.2% (means +/- SD) when cerulein was preceded by injection of octreotide at 12.5, 25, and 50 mg, respectively. These results indicate that octreotide is able to inhibit the plasma amino acid uptake by pancreatic acinar cells and, consequently, synthesis of pancreatic enzymes. Clinically, this effect could be useful in treatment of pathologic conditions of the pancreas in which it is desirable to suppress acinar cell activity and avoid accumulation of enzymes in acinar cells.
Pancreas 1991 Nov
PMID:Effect of octreotide, a long-acting somatostatin analogue, on plasma amino acid uptake by the pancreas. 178 Mar 27

Treatment of pancreatic pain remains a very difficult problem. At present, when the main pancreatic duct is dilated, lateral pancreaticojejunostomy remains the treatment of choice for refractory pancreatic pain. When the disease is localized to the head or tail of the pancreas, resection of these segments has also proven to be effective in the majority of patients. It will be important to learn whether medical strategy (such as treatment with oral pancreatic enzymes or somatostatin) and endoscopic techniques (such as insertion of stents or shock-wave lithotripsy), compare favorably with surgical techniques. This evaluation will require randomized prospective trials.
Pancreas 1991
PMID:Management of pancreatic pain. 178 53

This study was undertaken to determine the origin and forms of immunoreactive somatostatin (SLI) present in the pancreatic juice of cannulated nonanesthetized rats. The systemic origin of somatostatin (SS) was assessed from bolus intravenous injections of either I125-Tyr1-SS-14 or synthetic SS-14 under basal and stimulated pancreatic juice secretion, and from measurements of radioactivity and SS-14 in the collected juice. Gel filtration of pooled juice samples indicated that there were no forms of SS corresponding to standards of I125-Tyr1-SS-14 or SS-14, but radioactive material eluted in the area of either I125-Tyr or free iodine. Investigation of the presence of SS-14 in the juice by radioimmunoassay (RIA) led to the identification of a 23-kDa SS-like immunoreactive protein that did not correspond to any of the three known forms of SS present in the pancreatic tissue (Pro-SS, SS-28, and SS-14). By boiling the juice before the RIA, this 23-kDa protein was no longer detectable by RIA. These data suggest that this protein may be a "putative" enzyme, degrading the SS tracer in the RIA. This possibility is supported by the observation that boiled juice lost this capacity of interfering with the RIA. In conclusion, SS in the pancreatic juice, if present, is not from systemic origin and the juice contains an active thermosensitive substance degrading the SS tracer in the RIA.
Pancreas 1990 Mar
PMID:Origin and characterization of immunoreactive somatostatin in rat pure pancreatic juice. 196 58

We have investigated the influence of non-insulin-dependent diabetes on the regulation of somatostatin secretion from the pancreatic D cell. These results were compared with the concomittantly measured secretory responses from A and B cells. Rats were rendered non-insulin-dependent diabetic by neonatal injection of streptozotocin (STZ). Secretion was studied in perfused pancreas at 6-10 weeks of age. At this age, STZ rats were mildly hyperglycemic, their nonfasting blood glucose being 9.0 +/- 0.8 vs. 5.6 +/- 0.2 mM in control rats. In perfused pancreas from the latter rats, high glucose, i.e., 16.7 mM, stimulated somatostatin secretion but completely failed to do so in STZ rats. Arginine (in the presence of low glucose, i.e., 3.3 mM) moderately stimulated somatostatin secretion in controls but fourfold more in STZ rats. Preperfusion with high glucose markedly potentiated subsequent arginine-induced somatostatin secretion in controls but failed to do so in STZ rats. Basal glucagon release was inhibited by ambient high glucose in control and STZ rats alike. Arginine-induced glucagon release was profoundly inhibited both by ambient and previous exposure to glucose in controls but only slightly and nonsignificantly in STZ rats. The insulin response to high glucose in controls was reduced by 90% in STZ. The insulin response to arginine (in the presence of low glucose) was 3.3-fold enhanced in STZ. Ambient and previous high glucose markedly enhanced arginine-induced insulin secretion in controls but only moderately so in STZ rats. We conclude that already mild hyperglycemia is associated with marked D-cell insensitivity to glucose that is qualitatively similar to A- and B-cell insensitivity.
Pancreas 1990 May
PMID:Abnormal regulation by glucose of somatostatin secretion in the perfused pancreas of NIDDM rats. 197 41

We studied the effect of a primed i.v. infusion of somatostatin (100 micrograms as a bolus, 0.5 micrograms x kg-1 x min-1) on pancreatic exocrine secretion in response to electrical stimulation of the vagus nerves and intra-arterial infusions of acetylcholine (0.5 mg x min-1) in anesthetized pigs (17-22 kg). In control experiments, vagus stimulation and acetylcholine increased protein secretion 31- to 80-fold and 106-fold, respectively. Somatostatin inhibited the response to vagus stimulation by more than 90%, whereas the response to acetylcholine remained unaffected. It is concluded that the inhibitory action of somatostatin on the vagally induced secretion must be due to an inhibition of the impulse transmission in the efferent parasympathetic nerves to the pancreas, and it is suggested that this mechanism contributes to the inhibitory effect of somatostatin observed with other stimuli as well.
Pancreas 1990 Sep
PMID:Somatostatin inhibits neurally stimulated pancreatic secretion indirectly. 197 15

The purpose of the study was to examine the transhepatic and peripheral effects of somatostatin (SN) infusion on plasma glucose and insulin during insulin (IN) infusion. Hepatic blood flow was measured electromagnetically during intermittent sampling from the portal and hepatic veins, femoral artery, and right external jugular vein. Hepatic blood flow [sum of portal vein (PV) and hepatic artery] was similar during IN or IN + SN infusions. IN concentrations decreased in the portal vein from 374.8 +/- 50.3 to 295.8 +/- 25.9 pM (p less than 0.01) when SN was infused with IN. Hepatic venous plasma IN concentration also decreased from 143.6 +/- 26.6 to 88.3 +/- 10.1 pM (p less than 0.01). Plasma IN concentrations in the femoral artery and jugular vein remained unchanged. Hepatic insulin extraction changed from 64 +/- 4% during IN to 72 +/- 3% during IN + SN (p less than 0.01). Hepatic clearance and total body clearance were unchanged. Peripheral venous glucose with a nadir of 3.82 +/- 0.2 mM during IN alone decreased to a nadir of 3.16 +/- 0.27 mM (p less than 0.01) during IN + SN infusion. Mean portal venous glucose concentrations were 5.0 +/- 0.27 and 3.4 +/- 0.19 mM, respectively (p less than 0.01). In two additional experiments in which endogenous C-peptide concentrations were examined in the portal vein and femoral artery, C-peptide levels were lower during IN + SN compared to IN alone. We conclude that SN used to suppress endogenous insulin secretion increases hepatic insulin extraction, lowers glucose concentrations, and suppresses endogenous C-peptide levels to a greater extent than insulin infusion alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Pancreas 1990 Nov
PMID:The effect of somatostatin on insulin and glucose levels during insulin infusion in anesthetized dogs. 198 Jul 34

The BB/W strain of rats develop spontaneous insulin-dependent diabetes. Diabetic BB/W rats have a marked insulinopenia and greatly diminished levels of insulin in their pancreas. Using a radioimmunoassay for rat pancreatic polypeptide (PP), we have examined the content of PP in extracts of the total pancreas and also the regional PP concentration of the three pancreatic lobes. Radioimmunoassays for glucagon, somatostatin (SRIF) and insulin were also made on these extracts. Compared with nondiabetic BB/W rat pancreas, pancreatic extracts from severely diabetic BB/W rats contained 30% as much PP, 31% as much glucagon, 19% as much SRIF, and 0.5% as much insulin. The rat PP radioimmunoassay was used to determine the elution pattern of PP-like antigens in gel chromatography fractions and to measure in vitro secretion of PP from perifused pancreatic slices obtained from diabetic and nondiabetic animals. PP-like immunoreactivity was observed in two zones in the elution from the gel columns when extracts from normal or diabetic rats were chromatographed. The major zone of immunoreactivity eluting at the volume expected for intact monometric rat PP accounted for 67% of the PP-like immunoreactivity in the case of nondiabetic rats and greater than 80% of the PP-like immunoreactivity found in extracts from severely diabetic rats. The minor zone of PP-like immunoreactivity eluted at a volume similar to the position of tetradecapeptide SRIF contained the remainder of detected PP-like immunoreactivity. Tissue slices from diabetic rats secreted more PP and glucagon than slices from nondiabetic rats when slices were perifused with a medium containing leucine, carbachol, and cholecystokinin, even though diabetic pancreas has smaller amounts of PP, glucagon, SRIF, and insulin. Stimulated insulin secretion was virtually absent when tissue slices from diabetic rats were perifused. These results indicate that in the BB/W diabetic rat: (a) pancreatic glucagon, PP, and SRIF are moderately decreased and insulin levels are drastically reduced, (b) lower levels of degraded or low molecular weight form of immunoreactive PP occurs in the diabetic rat pancreas compared to the normal rat, (c) the diabetic pancreas secretes more PP and glucagon and much less insulin than pancreas from nondiabetic rats when perifused under stimulating conditions. The diabetes occurring in the BB/W appears to be a severe type I diabetes characterized by reduced content of insulin, glucagon, SRIF, and PP in the pancreas of these animals. However, secretion of glucagon and PP were not reduced in this in vitro system.
Pancreas 1990 Nov
PMID:Pancreatic polypeptide and other pancreatic hormones in spontaneously diabetic BB/W rats. 198 Jul 35

Novel islet cell, duct cell, and acinar cell markers have been identified by monoclonal autoantibodies (Maab) derived from prediabetic BB rats. Spleen cells from two rats that both developed diabetes after splenectomy were fused with mouse myeloma cells. A cellular immunoradiometric assay for differential reactivity toward the surface of two closely related, insulin- and non-insulin-producing rat islet tumor cell lines was used to select and clone several IgM-producing hybridomas. The supernatants were finally characterized by two-color immunofluorescence with islet hormone antisera on frozen sections of human, monkey, and rat pancreas. Maab EB52 stained PP cells, but also few A cells on rat pancreas. Maab CA812 identified a subpopulation of islet D cells on rat, human and monkey pancreas. Although the CA812-reactive antigen and somatostatin were coexpressed in most D cells in adult rat pancreas, only a few islet D cells were stained in the newborn pancreas. The CA812-reactive antigen was not detected in somatostatin-producing cells in the duct epithelium. Maab H37 and IF5 selectively stained acinar cells in rat, human, and monkey pancreas, whereas Maab DA39 identified the rat ductal epithelium including the scattered endocrine cells of the ducts. In summary, B lymphocytes producing autoantibodies to pancreatic endocrine, exocrine, and ductal markers are present in prediabetic BB rats and can be detected by use of transformed pluripotent islet cells as target. Such B lymphocytes can be immortalized to produce monoclonal antibodies to study their role in insulin-dependent diabetes mellitus pathogenesis and to clarify the development of the pancreas.
Pancreas 1990 Sep
PMID:Novel islet, duct, and acinar cell markers defined by monoclonal autoantibodies from prediabetic BB rats. 212 46

We studied the effects of SMS 201-995 (SMS), a somatostatin analog, and tamoxifen, an antagonist of estrogenic actions, on the growth of human pancreatic cancers (SKI and PGER) in vivo. Male nude mice were inoculated with either SKI or PGER by passage of tumor chunks (3 mm2) to the scapular region. Mice from each tumor group were randomly allocated to one of four treatment groups: group 1, control group; group 2, SMS (100 micrograms/kg t.i.d.); group 3, tamoxifen (10 mg/kg three times a week); and group 4, SMS (100 micrograms/kg t.i.d.) + tamoxifen (10 mg/kg three times a week). The somatostatin analog, SMS, given alone or as a combined regimen with tamoxifen, significantly reduced (a) the rate of growth of SKI, and (b) DNA, RNA, and protein content of the tumors. On the other hand, in the case of PGER tumors, none of the treatment regimens significantly influenced the growth of PGER in vivo. Despite showing no significant effects during the study, PGER tumors in mice receiving tamoxifen alone had significantly lower total DNA, RNA, and protein contents compared to control tumors; this was reversed on combined treatment with SMS. None of the growth parameters of PGER was effected by SMS alone. We conclude that, in the case of SKI, SMS with or without tamoxifen was effective as a growth inhibitory agent, whereas in the case of PGER, tamoxifen alone was effective. This finding suggests that independent pathways mediate the growth-inhibitory effects of tamoxifen and SMS, and that different pancreatic cancers may respond to the two agents differently, some with inhibition, some not.
Pancreas 1990 Mar
PMID:Effect of somatostatin and tamoxifen on the growth of human pancreatic cancers in nude mice. 215 57

In conscious pigs, i.v. infusion of serial doses of neurotensin (NT, actual doses of 0.24-59.4 pmol.kg-1.min-1) on a background of secretin resulted in a linear increase of plasma NT-like immunoreactivity (NT-LI), as measured with an antiserum that requires the biologically active C-terminal part of the molecule for recognition. The NT infusions were accompanied by a dose-related increase of pancreatic volume and bicarbonate and protein output. The threshold plasma NT-LI concentrations for significant increases of pancreatic enzymes and of pancreatic fluid and bicarbonate were 46.6 +/- 7.0 and 161.3 +/- 10.8 pM, respectively. Food intake was followed by a sharp pancreatic response and a progressive increase of plasma NT-LI level to a peak of about 27.7 +/- 3.0 pM from the basal level 11.8 +/- 1.6 pM. The carbohydrate fraction of the meal was predominantly responsible for the NT release observed after meal intake. High-performance liquid chromatography analysis of plasma samples collected during NT infusion or after meal ingestion revealed one immunoreactive peak coeluting with intact NT. Pancreatic polypeptide was released on infusion of high, supraphysiological doses of NT, while plasma somatostatin remained at low basal values. It is concluded that in the pig, intact NT is released after a standard meal predominantly through the carbohydrate fraction of the diet, NT is a stimulant of exocrine pancreas secretion, and the modest pancreatic response to physiologic increments of plasma NT-LI on peptide infusion is not attributable to indirect inhibition of the exocrine pancreas by NT-released pancreatic polypeptide or somatostatin.
Pancreas 1990 May
PMID:Plasma neurotensin in the conscious pig: release by individual food components and effects on exocrine pancreas secretion. 234 43


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