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 immunocytological method was used to investigate whether vasoactive intestinal peptide (VIP) is present in the pituitary gland and to localize the peptide at the cellular and subcellular levels. Pituitaries of Wistar male and female rats (Iffa Credo) were fixed in glutaraldehyde 2.5% and postosmicated and frozen in liquid nitrogen. Ultrathin slices, obtained by cryo-ultramicrotomy were incubated with the antiserum. The antigen-antibody reaction was detected by peroxidase-antiperoxidase complexes revealed by 4-chloro-1-naphtol. The prolactin (PRL)-secreting cells were identified by using an anti-oPRL antiserum. The PRL immunoreactivity was localized in secretory granules of irregular shapes. An anti-VIP serum was used which neither cross-reacted with the several fragments of VIP molecule nor with peptides from gut or hypothalamus. The VIP immunoreactivity obtained with this antiserum, was observed in PRL cells only but never in so-matotropic, gonadotropic, corticotropic and thyrotropic cells. The immunoreactivity was localized in the cytoplasmic matrix between and around the secretory granules but not in the organelles, and in the nucleus distributed all over the euchromatin near to the heterochromatin regions. No reaction was observed by using either nonimmune serum or anti-VIP antiserum incubated with VIP. No modification of VIP immunoreactivity was observed by using anti-VIP antiserum incubated with somatostatin, gonado- or thyroliberin. These data (1) provide immunocytological evidence for presence of VIP in pituitary gland; (2) indicate the presence of this peptide in one particular pituitary cell type, and (3) support the hypothesis that VIP could have a direct effect on the control of PRL secretion.
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PMID:Ultrastructural evidence for endogenous vasoactive intestinal peptide-like immunoreactivity in the pituitary gland. 707 May 88

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

Impairments of both basal and insulin-stimulated oxidative (Gox) and nonoxidative (Nox) glucose metabolism are documented to exist in non-insulin-dependent diabetes mellitus (NIDDM). Although these defects have been well characterized during insulin stimulation, little is known about the effects of basal insulin or its deficiency on intracellular glucose metabolism in NIDDM. To determine the physiological significance of basal insulin in the maintenance of glucose metabolism in NIDDM, we studied nine subjects with NIDDM in the basal and insulin-deficient state produced by 3 hours of somatostatin (SRIF) infusion (0.08 pmol/kg/min). Glucose turnover rates were quantified by [3-3H]glucose turnover, and substrate oxidation was assessed by a combination of indirect calorimetry and urinary nitrogen measurements. Skeletal muscle glycogen synthase (GS) and pyruvate dehydrogenase (PDH) activities were also measured in the basal state and during SRIF infusion. Basal glucose levels were maintained during SRIF infusion by exogenous glucose infusion (12.5 +/- 0.9 mmol/L in the basal state v 12.8 +/- 0.8 during SRIF infusion, P = NS). During the last hour of SRIF infusion, plasma C-peptide levels declined by 88% from 0.73 +/- 0.11 to 0.09 +/- 0.02 nmol/L (P < .001), and serum insulin concentrations were undetectable (< 14 pmol/L). During insulinopenic conditions, rates of glucose uptake (GU) were decreased by 12% from basal level of 2.26 +/- 0.13 to 1.99 +/- 0.12 mg/kg/min (P < .05), and were entirely accounted for by reduced rates of Gox (1.01 +/- 0.10 to 0.65 +/- 0.14 mg/kg/min, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of basal insulin in maintenance of intracellular glucose metabolic pathways in non-insulin-dependent diabetes mellitus. 785 64

Fetal leucine oxidation rate is elevated during fasting of the ewe. Euglycemic hyperinsulinemia causes the leucine oxidation rate to decline. However, it is unclear whether this is a direct effect of insulin or is secondary to increased insulin-mediated glucose utilization. To better delineate the mechanism of decreased oxidation, we suppressed fetal insulin secretion by somatostatin infusion. Glucose was infused at a variable rate to achieve glucose concentrations 125 and 150% of basal. Leucine rate of appearance (Ra) was determined by infusion of [15N, 1-13C]leucine. Fraction of leucine appearance oxidized was determined by [1-14C]leucine infusion and determination of fetal 14CO2 excretion. Each fetus was studied during ad libitum maternal feeding and after a 5-day complete maternal fast. Changes were noted in fetal leucine oxidation, which declined from 8.4 +/- 1.2 to 5.0 +/- 0.8 mumol/min in the fed state during glucose infusion. Basal leucine oxidation was elevated during fasting (11 +/- 1.5 mumol/min, P < 0.05) and declined to 8.0 +/- 1.4 mumol/min during glucose infusion (P = 0.056). Leucine carbon Ra was unchanged by fasting and by glucose infusion; leucine nitrogen Ra declined in the fed state only. Leucine oxidation was inversely correlated with glucose concentration (oxidation = 12-0.26 x glucose concentration, r = 0.42, P = 0.004). Leucine oxidation was not correlated with insulin concentration (r = 0.2). Changes in fetal glucose concentration may alter the pattern of utilization of essential amino acids, independent of changes in insulin and insulin-mediated glucose utilization rate.
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PMID:Increased fetal glucose concentration decreases ovine fetal leucine oxidation independent of insulin. 790 97

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

The relative contribution of hyperglucagonemia to the mechanisms of nitrogen loss during catabolic states has not been clearly established. The present study examines the independent effect of physiologic elevations of plasma glucagon on whole-body protein kinetics, as well as on net amino acid balance across the liver and gastrointestinal tract tissues, in conscious 18-hour-fasted dogs (n = 7). Each study consisted of a 120-minute equilibration period, a 30-minute basal period, and a 150-minute experimental period. Leucine kinetics were measured using L-[1-14C]leucine. Pancreatic hormones were maintained by infusing intravenous somatostatin (0.8 micrograms/kg.min), intraportal insulin (275 microU/kg.min), and intraportal glucagon (0.65 ng/kg.min basally and 2.5 experimentally). Dextrose was infused to maintain plasma glucose constant (14.1 +/- 0.3 mumol/L), thereby providing a consistent metabolic steady state for the study of protein and amino acid metabolism. In the experimental period, plasma glucagon was fourfold basal levels (112 +/- 10 v 32 +/- 6 pg/mL), whereas plasma insulin remained stable (mean, 10 +/- 1 microU/mL). Hepatic glucose production was increased 30%, but leucine rates of appearance ([Ra] proteolysis), oxidative disappearance (Rd), and nonoxidative Rd (protein synthesis) were not altered during the experimental period. Furthermore, the net release of amino acids by the gastrointestinal tract was not increased by glucagon. However, uptake and extraction of amino acids by the liver were increased, resulting in a 17% decrease in total plasma amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of glucagon in the control of protein and amino acid metabolism in vivo. 799 Jul 4

Two recent developments in the medical treatment of patients with pituitary disease are discussed. Conventional treatment for patients with acromegaly has been surgery and/or radiotherapy. Dopamine agonist therapy may be useful. Somatostatin is a naturally occurring neuropeptide that inhibits growth hormone (GH) secretion. The development of long-acting preparations has resulted in a considerable advance in the medical treatment of acromegaly, though some caution remains about the long-term side-effects of such therapy (e.g. cholelithiasis) and its cost/benefit analysis. Although further epidemiological studies are required, hypopituitarism appears to be associated with an increased mortality rate, and this has largely been attributed to GH deficiency. With the widespread availability of recombinant GH (thereby circumventing any risks from cadaveric GH) many adult GH-deficient patients are now being treated. Beneficial effects on body composition, nitrogen and calcium balance and bone mass have already emerged, although studies on 'well being' have been conflicting. The debate continues concerning the minimum effective dose and who exactly should be treated, in view of the costs incurred. The endocrinologists' use of long-acting somatostatin analogues and recombinant GH will undoubtedly increase over the next few years. Whilst it is clear that many patients with both acromegaly and hypopituitarism will benefit, long-term controlled trials are still required to establish firmly the benefit in terms of major morbidity.
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PMID:Advances in medical therapy for pituitary disease: treating patients with growth hormone excess and deficiency. 810 42

Intravenous fluid requirements for patients with permanent end-jejunostomy syndrome often exceeds 3 L/d, making rehabilitation difficult. The effect of the somatostatin analogue, octreotide (100 micrograms TID, subcutaneously) in reducing requirements was measured in 10 patients established on home parenteral nutrition. After 10 days of treatment, 72-hour balance measurements demonstrated significant reductions in stomal fluid and electrolyte losses from (mean +/- SE) 8.1 +/- 1.8 to 4.8 +/- 0.7 L/d (p < .03), sodium from 510 +/- 71 to 340 +/- 41 mEq/d (p < .03), chloride from 533 +/- 70 to 315 +/- 32 mEq/d (p < .002), and potassium from 101 +/- 41 to 79 +/- 34 mEq/d (p < .02), permitting an average reduction in intravenous fluid requirements of 1.3 L/d (p < .0003), 118 mEq Na+/d (p < .03), 41 mEq K+/d (p < .02), and 178 mEq Cl-/d (p < .01). This meant that daytime intravenous infusions could be stopped in all patients. Fecal nitrogen losses were decreased (p < .05), but overall there was no significant change in fat and caloric absorption. In addition, hormonal stimulated gastric acid and pancreatic lipase secretions were significantly reduced (p < .05). The effect was most marked in those patients with massive stomal losses and uncontrollable thirst. Continuation of treatment for more than 1 year in 8 of the patients suggested preservation of potency and good tolerance, with the possible exception of accelerated gallstone formation and subacute intestinal obstruction. In conclusion, octreotide has the potential to improve the quality of life of those end-jejunostomy syndrome patients with massive stomal losses, resistant to conventional medical treatment.
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PMID:Octreotide as an adjunct to home parenteral nutrition in the management of permanent end-jejunostomy syndrome. 816 99

The anabolic actions of GH are well known, although specific tissue responses and the mechanism of nitrogen conservation are less well understood. This study was designed to examine the acute metabolic effects of GH on whole body and regional protein metabolism, using an experimental protocol which controlled for confounding perturbations in other hormones by a simultaneous infusion of somatostatin. Control subjects received replacement doses of insulin, glucagon, and GH for the entire 7-h study period, whereas GH subjects received an identical protocol, except for an increased dose of GH sufficient to increase serum concentrations into the high-physiological range (12-20 ng/mL) for the final 3.5 h of the study (P < 0.001). Thirteen young, healthy male subjects were studied in the postabsorptive period; five served as control subjects and eight as treatment (GH) subjects. Each received continuous iv infusions of somatostatin, L-[13-C]leucine, and L-[2H5]phenylalanine throughout the study. Femoral arterial and venous sampling allowed for simultaneous measurements across the leg and in the whole body. C-Peptide levels were suppressed throughout the infusion; insulin, glucagon, insulin-like growth factor I, cortisol, epinephrine, norepinephrine, and glucose concentrations were not different between groups. Glycerol concentrations increased 3-fold in GH subjects during the final 3.5-h period (P = 0.04). Concentrations of several amino acids declined through the study, but no differences were observed between treatment groups. Leucine oxidation was reduced in GH compared to control subjects (P = 0.04). No changes in CO2 production or whole body leucine or phenylalanine flux were observed, whereas nonoxidative disposal of leucine was marginally higher in GH compared to control subjects (P = 0.07). By contrast, rates of appearance and disappearance of both leucine and phenylalanine across the leg all were relatively lower in GH compared to control subjects; leucine balance across the leg was reduced by GH (P = 0.03), whereas phenylalanine balance was not influenced by GH. Our data thus demonstrate an acute stimulatory effect of GH on lipolysis, a decrease in leucine oxidation, and no stimulation of muscle protein synthesis in spite of enhanced protein synthesis in nonmuscle tissue.
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PMID:Acute growth hormone effects on amino acid and lipid metabolism. 817 57


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