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 importance of glucagon on postoperative changes in hepatic amino-nitrogen conversion were investigated in six patients undergoing elective cholecystectomy for uncomplicated gall stones. Patients were given infusions of somatostatin (bolus of 6 micrograms/kg followed by continuous infusion of 6 micrograms/kg/h) from induction of anaesthesia to the end of investigation, the first postoperative day (30 hours). Controls were 16 patients undergoing the same procedures omitting the somatostatin infusion. In all patients blood concentration and plasma clearance of total alpha-amino-nitrogen, and amino acid stimulated rate of urea synthesis were measured. Elective cholecystectomy decreased blood alpha-amino-nitrogen concentration from mean (SEM) 2.9 (0.2) to 2.4 (0.1) mmol/l (p < 0.05), increased the clearance of total alpha-amino-nitrogen from 5.2 (0.3) to 6.6 (0.3) ml/s (p < 0.05), and increased the rate of amino acid stimulated urea synthesis from 27 (1) to 37 (2) mumol/s (p < 0.05) pointing to increased hepatic removal of amino-nitrogen at expense of plasma amino-nitrogen. Infusion of somatostatin prevented increase of glucagon for 24 hours after surgery, and prevented the negative changes in postoperative nitrogen homeostasis resulting from the postoperative changes in hepatic nitrogen conversion, suggesting glucagon as mediator. The exact mechanism remains in doubt, however, because of the multiple effects of somatostatin.
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PMID:Somatostatin prevents the postoperative increases in plasma amino acid clearance and urea synthesis after elective cholecystectomy. 779 29

We investigated the inhibitory effect of insulin and glucose on hepatic amino- to urea-nitrogen conversion independent of endogenous insulin and glucagon secretion. Alanine-stimulated urea synthesis kinetics, as quantified by functional hepatic nitrogen clearance, i.e. the slope of the linear relation between blood alpha-amino nitrogen concentration and urea synthesis rate, were measured four times in each of six healthy volunteers, namely during spontaneous hormone responses, and during hormonal control by somatostatin and maintenance of basal hormone levels and euglycaemia, hyperinsulinaemia (85 +/- 8 mU/l), or hyperglycaemia (8.4 +/- 0.5 mmol/l). Hormonal control and euglycaemia reduced functional hepatic nitrogen clearance (mean +/- SD) by two-thirds (from 32.9 +/- 5.2 l/h to 12.2 +/- 3.4 l/h, p < 0.01). Hyperinsulinaemia did not change this (13.2 +/- 2.8 l/h), whereas hyperglycaemia further reduced functional hepatic nitrogen clearance by 40% to 7.4 +/- 1.3 l/h (p < 0.01). The reduction by hormonal control and euglycaemia is attributable to the abolition of the glucagon response to alanine infusion, as glucagon is known to up-regulate functional hepatic nitrogen clearance. Insulin did not regulate hepatic amino- to urea-nitrogen conversion, implying that the effect of insulin on urea production is due to its effect on blood amino acid supply to the liver. In contrast, glucose in itself reduced hepatic amino nitrogen conversion, independent of the hormonal responses to glucose. This means that the hepatic component of the amino-N-sparing effect of glucose depends on hyperglycaemia but not on hyperinsulinaemia.
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PMID:Effects of insulin and glucose on urea synthesis in normal man, independent of pancreatic hormone secretion. 783 8

Helicobacter pylori is a microaerophilic bacterium initially found in the gastric antrum of patients with peptic ulcer disease. As a result, H. pylori is now believed to have a pathophysiologic role in gastritis as well as in peptic ulcer disease. Several recent studies showed that it may be associated with duodenal ulcer relapse and that eradication therapy using antibiotics may significantly decrease the ulcer recurrence rate in duodenal ulcer patients. Moreover, epidemiological studies suggest that it may increase the relative risk of carcinoma in the stomach and preliminary studies seem to indicate that some low-grade lymphoma in the stomach may regress after H. pylori eradication. Although the mechanisms by which H. pylori induces mucosal injury and/or neoplasm is not clearly understood, several modifications in gastric functions have been reported. The most specific way of detecting H. pylori in tissue is a combination of culture and histologic staining of mucosal biopsy specimens obtained by endoscopy. Rapid urease test, cytology and PCR procedures performed on biopsies may give rapid, sensitive and specific results. Breath test using 13C- or 14C-radiolabelled urea and serology tests are of particular importance when H. pylori diagnosis is needed via no invasive procedures. Helicobacter pylori is supposed to interact with G and D cells. Gastrin and somatostatin are synthetized and released from antral G and gastric D cells respectively. The gastric D cells are in close contact with either G and parietal cells. Gastrin stimulates gastric acid secretion and epithelial gastric cell proliferation (parietal and EC-L cells) while somatostatin inhibits these effects. Chronic gastritis is associated with fundic duodenal ulcer disease. In this situation, basal gastrin and meal- or bombesin-stimulated gastrin in the serum (especially gastrin G17) have been found to be higher in H. pylori positive than in negative patients. Moreover, gastrin decreases up to normal levels after eradication of H. pylori. The long term effect of a such hypergastrinemia is not so far established. The mechanism underlaying hormonal modification is poorly understood. Since no G/D cell ratio modification could be found after H. pylori eradication while the amount of somatostatin increases, one would suggest functional alteration of either G or D cells in the H. pylori-related chronic gastritis. The role of inflammatory mediators on the gastrin release and the processing of progastrin induced by the bacterium need further investigations.
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PMID:[Helicobacter pylori, a rediscovered bacterium. Implication in gastroduodenal diseases]. 789 50

Glucose reduces the hepatic conversion of aminonitrogen to urea, quantified by the functional hepatic nitrogen clearance (i.e., the slope of the linear relation between urea synthesis rate and blood alpha-aminonitrogen concentration). This is due to a direct effect of glucose and to inhibition of glucagon. In this study, the effect of glucose on functional hepatic nitrogen clearance was examined during spontaneous hormone responses and during hormonal control by somatostatin. In 7 control subjects (study 1) and 9 patients with cirrhosis (study 2), functional hepatic nitrogen clearance was assessed twice in each subject: during infusion of alanine and during alanine administration superimposed on a continuous glucose infusion (blood glucose, on average = 8.4 mmol/L). In study 3, 6 patients with cirrhosis had functional hepatic nitrogen clearance determined on three occasions: during infusions of alanine and of alanine superimposed on infusion of somatostatin with either euglycemia or hyperglycemia (blood glucose = 8.4 mmol/L). In the control subjects (study 1), functional hepatic nitrogen clearance was 32.5 +/- 1.9 L/hr, and glucose reduced it to 18.4 +/- 0.9 L/hr (p < 0.01). In the cirrhotic patients, functional hepatic nitrogen clearance was only 9.8 +/- 1.3 L/hr (p < 0.01 vs. controls), and glucose did not change it. In the control subjects, glucose reduced the glucagon response to alanine from 204 +/- 36 ng/L to 106 +/- 8 ng/L (p < 0.05). In the cirrhotic patients the mean fasting glucagon level was increased twofold (180 +/- 21 ng/L). The response to alanine increased to 968 +/- 265 ng/L; it was not reduced by glucose. In study 3, somatostatin and hyperglycemia reduced functional hepatic nitrogen clearance from 13.2 +/- 1.5 L/hr to 6.4 +/- 0.7 L/hr (p < 0.01). Somatostatin and euglycemia reduced functional hepatic nitrogen clearance to 9.2 +/- 1.2 L/hr (p < 0.01 vs. alanine and hyperglycemia). The results show that the reduction by glucose of hepatic aminonitrogen conversion is lost in cirrhotic patients. The markedly increased glucagon response to alanine was not suppressed by glucose. Inhibition of the glucagon response by somatostatin reestablished the glucose effect, which was in part due to inhibition of glucagon in itself. Thus hepatic aminonitrogen conversion in cirrhosis depends on increased glucagon levels. The hormone-independent effect of glucose is preserved if the hyperglucagonemia is abolished, but the spontaneous high glucagon level overrules the glucose effect. The results indicate reduced hepatic contribution to the nitrogen-sparing effect of glucose in cirrhotic patients.
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PMID:Effects of glucose on hepatic conversion of aminonitrogen to urea in patients with cirrhosis: relationship to glucagon. 790 54

Four Suffolk wether lambs were used in a crossover design to determine the effects of a 3-d feed and water deprivation period on metabolic and hormonal responses to a glucose load. During each period of the crossover design all lambs were limit-fed a 36% concentrate diet for 16 d then two lambs were deprived of feed and water for 3 d. All lambs were then limit-fed the 36% concentrate diet. Glucose loading tests were performed before feeding on d 1, 5, and 9 of the realimentation period. Ten milliliters of a 2.5 M glucose solution were infused into the right jugular vein and blood samples were obtained from the left jugular vein at intervals for 4 h after infusion. Plasma or serum samples were analyzed for insulin, growth hormone (GH), somatostatin, prolactin, glucose, free fatty acids (FFA), and urea N. At the end of the period in which feed was withheld, fed lambs had greater (P < .09) serum insulin and lower plasma FFA (P < .01) and somatostatin (P < .05). On d 1 of realimentation, previously unfed lambs had greater postinfusion GH (P < .01), FFA (P < .01), and glucose (P < .04) concentrations. Previously unfed lambs also had a slower (P < .01) glucose fractional removal rate and longer (P < .02) glucose half-life than fed lambs on d 1 of realimentation, but they had a shorter (P < .13) glucose half-life than fed lambs on d 5 of realimentation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of a glucose load in fed or unfed lambs on blood metabolites and hormone patterns. 809 4

To determine the effects of hyperglycemia and hyperinsulinemia on lactate production by adipocytes, healthy volunteers were studied during three experimental protocols. In protocol 1, the changes in interstitial lactate concentrations were measured by microdialysis (sc tissue) after oral glucose administration. The plasma lactate concentration increased by 39.4 +/- 6.0%, and the dialysate lactate concentration increased by 117.9 +/- 16.3%. In protocol 2, a 2.5-h hyperinsulinemic euglycemic clamp and somatostatin infusion were performed. The plasma and dialysate lactate concentrations increased by 27.1 +/- 5.5% and 146.8 +/- 44.5%, respectively. In addition, [U-13C]glucose was infused through the probe, and dialysate lactate was enriched in 13C at 2.5 +/- 0.3 molar percent excess basally and at 3.4 +/- 0.3 molar percent excess during the clamp (P < 0.05 vs. basal). [13C]Urea was also infused through the probe, and the outflow to inflow ratio of [13C]urea was used as an index of local blood flow. It decreased by 10.2 +/- 3.6% (P < 0.001) at the end of the hyperinsulinemic euglycemic clamp, indicating an increase in blood flow. In protocol 3, a hyperglycemic clamp (10.0 mmol/L) at the basal insulin concentration was performed. It increased the dialysate lactate concentration by 43.5 +/- 15.9% and did not alter the plasma lactate concentration or local blood flow. It is concluded that hyperinsulinemia and, to a lesser extent, hyperglycemia stimulate glucose conversion into lactate in adipocytes. Hyperinsulinemia, but not hyperglycemia, also increases adipose tissue blood flow.
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PMID:Effects of hyperinsulinemia and hyperglycemia on lactate release and local blood flow in subcutaneous adipose tissue of healthy humans. 876 47

Diet protein increases whereas carbohydrates decrease urea synthesis. Traditionally, these effects have been explained by changes in substrate supply. Diet protein intake increases whereas carbohydrate decreases blood amino acid concentration. However, glucose also decreases urea synthesis by a hepatic mechanism independent of the decrease in blood amino acid concentration. Whether this is due to an effect of glucose in itself, or whether the fall in glucagon or the rise in insulin is responsible, was not known. This survey deals with the effect of an increase in diet protein intake and of the separate effects of glucose, glucagon and insulin on functional hepatic nitrogen clearance in normal man and in patients with cirrhosis of the liver. The functional hepatic nitrogen clearance is calculated as the slope of the linear regression analysis of alanine-stimulated urea synthesis rate and blood alpha-amino nitrogen concentration, and expresses urea synthesis independent of changes in blood amino acid concentration. In patients with cirrhosis, hepatic nitrogen clearance is reduced in parallel with liver cell mass, despite high glucagon concentration that would normally up-regulate the process. In both healthy subjects and in patients with cirrhosis, an increase in diet protein intake (plus approximately 50 g/day) for 14 days increases hepatic nitrogen clearance by 40%. Thus, in addition to the substrate effect, protein intake increases urea synthesis by an effect in the liver, probably by enzyme formation. What induces this is not clear but high postprandial levels of glucagon may be involved. Although the effect is qualitatively intact in the patients, the response relative to the increase in protein intake is reduced by two-thirds. The effect may be important to control blood amino acid concentration during a high protein diet and may partly explain why patients with cirrhosis usually tolerates protein hyperalimentation without developing hepatic encephalopathy. It is shown that the reduction of hepatic nitrogen clearance by glucose depends on hyperglycaemia, and is accomplished by the additive effects of a direct hormone-independent action of glucose, and indirectly via suppression of glucagon. Insulin is not a direct controller of hepatic nitrogen clearance, but is still considered an important regulator of urea synthesis by its reducing effects on blood amino acid concentration. High experimental glucagon levels overrule the normal suppressive effect of glucose. In contrast, it is shown that the sugar-alcohol xylitol normalises the glucagon induced increase in hepatic nitrogen clearance. During normal glucagon levels xylitol exerts only a very little decrease in hepatic nitrogen clearance. In patients with cirrhosis, glucose does not down-regulate hepatic nitrogen clearance. However, when the spontaneous high glucagon levels are normalised by somatostatin, glucose decreases hepatic nitrogen clearance. This shows that the direct hormone-independent effect of glucose is intact. These findings indicate that the high glucagon levels during spontaneous hormone responses overrule the suppressive effect of glucose. Incomplete glucose suppression of glucagon secretion during alanine infusion contributes to the high glucagon levels. The removal of the high glucagon levels decreases hepatic nitrogen clearance in itself. Thus, the hyperglucagonaemia may be a compensatory mechanism by which the cirrhotic liver to some extent reestablishes its capacity to produce urea. The consequence is the defective down-regulation of hepatic nitrogen clearance by glucose. The reduction in urea synthesis by glucose, i.e. its nitrogen sparing effect, is accomplished by two different mechanisms: A hepatic component (reduction of the hepatic nitrogen clearance) and a peripheral component (reduced substrate availability mediated by the insulin response). This is an extension of former thoughts according to which glucose reduces urea synthesis due solely to
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PMID:Regulation of urea synthesis by diet protein and carbohydrate in normal man and in patients with cirrhosis. Relationship to glucagon and insulin. 923 44

Utilizing NNC 26-9100 (11) as a structural lead, a variety of nonpeptide derivatives of somatostatin were synthesized and evaluated for sst2 and sst4 receptor binding affinity. A novel thiourea scaffold was utilized to attach (1) a heteroaromatic nucleus to mimic the Trp8 residue, (2) a nonheteroaromatic nucleus to mimic Phe7, and (3) a primary amine or other basic group to mimic the Lys9 residue of somatostatin. Displacement studies were carried out using membranes from cell lines expressing ssts [BHK cells (sst4) and HEK 293 cells (sst2)] utilizing [125I]Tyr11-SRIF as the radioligand. Several thioureas (11, 38, 39, 41, and 42) and the urea 66 exhibited Ki values of less than 100 nM. The thioureas 11 (Ki = 6 nM) and 41 (Ki = 16 nM) and the urea 66 (Ki = 14 nM) are believed to be the most potent nonpeptide sst4 agonists known. Since the thiourea 11 and the urea 66 exhibit high sst4 selectivity, these novel nonpeptide derivatives may be useful tools for studying the sst4 receptor. Studies are currently in progress to evaluate the therapeutic potential of NNC 26-9100 (11) in the treatment of glaucoma.
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PMID:Nonpeptide somatostatin agonists with sst4 selectivity: synthesis and structure-activity relationships of thioureas. 982 40

The protection of Helicobacter pylori from the gastric acid exerted by urease is based on an increase of the bacterial periplasmic pH and membrane potential. Ammonia generated from urea induces apoptosis of gastric cells in vitro, and inhibits gastric somatostatin release in animals, which could have consequences on the physiology of digestion in general. The type s1/m1 structure of the vacA gene is associated with the production of high levels of cytotoxin. Strains with m2 region type, formerly considered devoid of toxic activity, are fully toxic when assayed with cell lines other than HeLa cells, which possibly lack receptors for m2 VacA type. The enhanced gastric mucosa damage associated with infection by cytotoxic organisms could be explained by the varying of effects exerted by VacA on target cells: extracellular secretion of acidic hydrolases, cytoskeletal alterations, actin rearrangement, reduction of epidermal growth factor binding to its receptor, inhibition of the stimulation of CD4+ T cells proliferation induced by the antigen presenting cells. Organisms that possess the pathogenicity island cag (cag+) induce an increased inflammation and transduction of signals to the host cells; however, they reduce the apoptosis of colonised cells. The results of an investigation on the possible influence of a variable cagA status on the extension of apoptosis have indicated that this kind of programmed death is disengaged from the possession of cagA by Helicobacter pylori organisms colonising the same gastric areas. It is likely that the whole pathogenic potential of cag+ organisms is far from being completely explored, as suggested by the recent finding that the expression of a bacterial adhesin (called BabA) involved in binding to the blood group antigen Lewis b is associated with the presence of cag.
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PMID:New acquisitions in Helicobacter pylori characteristics. 1007 48

Backbone cyclization of urea-based somatostatin agonists resulted in novel, orally bioavailable agonists. Binding assays confirmed that the resulting conformationally constrained cyclic ureas retained the potency of their acyclic counterparts. SAR studies subsequently led to highly potent analogs, selective for receptor subtype 2, and having good oral bioavailability.
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PMID:Potent, orally bioavailable somatostatin agonists: good absorption achieved by urea backbone cyclization. 1009 8


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