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 aim of this study was to determine the role of glucagon in hepatic glutamine (Gln) metabolism during exercise. Sampling (artery, portal vein, and hepatic vein) and infusion (vena cava) catheters and flow probes (portal vein, hepatic artery) were implanted in anesthetized dogs. At least 16 days after surgery, an experiment, consisting of a 120-min equilibration period, a 30-min basal sampling period, and a 150-min exercise period, was performed in these animals. [5-(15)N]Gln was infused throughout experiments to measure gut and liver Gln kinetics and the incorporation of Gln amide nitrogen into urea. Somatostatin was infused throughout the study. Glucagon was infused at a basal rate until the beginning of exercise, when the rate was either 1) gradually increased to simulate the glucagon response to exercise (n = 5) or 2) unchanged to maintain basal glucagon (n = 5). Insulin was infused during the equilibration and basal periods at rates designed to achieve stable euglycemia. The insulin infusion was reduced in both protocols to simulate the exercise-induced insulin decrement. These studies show that the exercise-induced increase in glucagon is 1) essential for the increase in hepatic Gln uptake and fractional extraction, 2) required for the full increment in ureagenesis, 3) required for the specific transfer of the Gln amide nitrogen to urea, and 4) unrelated to the increase in gut fractional Gln extraction. These data show, by use of the physiological perturbation of exercise, that glucagon is a physiological regulator of hepatic Gln metabolism in vivo.
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PMID:Glucagon response to exercise is critical for accelerated hepatic glutamine metabolism and nitrogen disposal. 1095 Aug 33

Veal calves fed by bucket often develop postprandial insulin resistance, hyperglycemia, and glucosuria during fattening. Automatic feeding systems allow feed intake for 24 h, and small ingested portions are expected to decrease postprandial glucose loads. We have studied metabolic and endocrine traits in calves that were either 1) fed identical daily amounts of whole milk plus milk replacer by a computer-programmed automatic feeder (> or =6 portions from 0800 to 2400 h) (GrA) or 2) fed by bucket at 0800 and 1630 h (GrB). Calves started at a body weight of 118 kg, and the experiment lasted for 3 wk. During wk 3, lactose was supplemented to stress postabsorptive glucose homeostasis. Feed intake and average daily gains in GrA and GrB were similar. Plasma concentrations during an 8-h period of glucose (in part), lactate, urea, and somatostatin (in wk 3), and of glucagon and insulin (wk 2 and 3) were smaller in GrA than in GrB, whereas growth hormone, insulin-like growth factor I, insulin-like growth factor binding protein-1 (wk 2), and prolactin concentrations (wk 2 and 3) were higher. Lactose supplementation in wk 3 enhanced transient postprandial hyperglycemia and hyperinsulinemia. Thus, there were marked metabolic and endocrine differences when calves sucked their feed in six or more portions during a 16-h period from an automatic feeder compared with twice daily drinking from a bucket. Ingestion of small portions by calves avoided marked hyperglycemia and lactate increments, and lower plasma urea concentrations mirrored enhanced nitrogen utilization, possibly mediated by the altered growth hormone, IGF-I and insulin status.
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PMID:Postprandial metabolism and endocrine status in veal calves fed at different frequencies. 1110 67

The metabolic response to fasting involves a series of hormonal and metabolic adaptations leading to protein conservation. An increase in the serum level of growth hormone (GH) during fasting has been well substantiated. The present study was designed to test the hypothesis that GH may be a principal mediator of protein conservation during fasting and to assess the underlying mechanisms. Eight normal subjects were examined on four occasions: 1) in the basal postabsorptive state (basal), 2) after 40 h of fasting (fast), 3) after 40 h of fasting with somatostatin suppression of GH (fast-GH), and 4) after 40 h of fasting with suppression of GH and exogenous GH replacement (fast+GH). The two somatostatin experiments were identical in terms of hormone replacement (except for GH), meaning that somatostatin, insulin, glucagon and GH were administered for 28 h; during the last 4 h, substrate metabolism was investigated. Compared with the GH administration protocol, IGF-I and free IGF-I decreased 35 and 70%, respectively, during fasting without GH. Urinary urea excretion and serum urea increased when participants fasted without GH (urea excretion: basal 392 +/- 44, fast 440 +/- 32, fast-GH 609 +/- 76, and fast+GH 408 +/- 36 mmol/24 h, P < 0.05; serum urea: basal 4.6 +/- 0.1, fast 6.2 +/- 0.1, fast-GH 7.0 +/- 0.2, and fast+GH 4.3 +/- 0.2 mmol/1, P < 0.01). There was a net release of phenylalanine across the forearm, and the negative phenylalanine balance was higher during fasting with GH suppression (balance: basal 9 +/- 3, fast 15 +/- 6, fast-GH 17 +/- 4, and fast+GH 11 +/- 5 nmol/min, P < 0.05). Muscle-protein breakdown was increased among participants who fasted without GH (phenylalanine rate of appearance: basal 17 +/- 4, fast 26 +/- 9, fast-GH 33 +/- 7, fast+GH 25 +/- 6 nmol/min, P < 0.05). Levels of free fatty acids and oxidation of lipid decreased during fasting without GH (P < 0.01). In summary, we find that suppression of GH during fasting leads to a 50% increase in urea-nitrogen excretion, together with an increased net release and appearance rate of phenylalanine across the forearm. These results demonstrate that GH-possibly by maintenance of circulating concentrations of free IGF-I--is a decisive component of protein conservation during fasting and provide evidence that the underlying mechanism involves a decrease in muscle protein breakdown.
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PMID:The protein-retaining effects of growth hormone during fasting involve inhibition of muscle-protein breakdown. 1114 1

DOTA-D-Phe1-Tyr3-octreotide (DOTATOC), a newly developed somatostatin analogue which can be stably labelled with the beta-emitter yttrium-90, can be used for receptor-mediated internal radiotherapy. A 78-year-old woman suffering from a carcinoid of the small intestine with multiple metastases in the liver as well as mesenteric and supraclavicular lymph node metastases was treated with this therapy after the disease had progressed under other chemotherapy options employed years previously. The patient received four single doses of 90Y-DOTATOC at 6-week intervals, yielding a cumulative dose of 9,620 MBq (5,659 MBq/m2). Restaging revealed stable metastatic disease. Serum creatinine and urea nitrogen levels were within the normal range prior to starting and during DOTATOC therapy. However, 15 months after cessation of DOTATOC therapy, a progressive deterioration of renal function occurred, leading to end-stage renal disease. Urinalysis revealed a slight proteinuria of 700 mg/day without haematuria, leucocyturia or casts. There was no obvious risk factor for chronic renal insufficiency except DOTATOC therapy. However, it was not feasible to use kidney biopsy to prove the presence of radiation-induced nephritis. Intermittent haemodialysis was started as the creatinine clearance declined to below 10 ml/min. Diuresis was not affected. The presented case shows delayed renal insufficiency after a relatively low cumulative dose of 90Y-DOTATOC (5,659 MBq/m2). This serious adverse event indicates that further studies are needed to evaluate which dose of 90Y-DOTATOC, under which renal protection regimen, will provide optimal management, balancing risks and benefits.
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PMID:End-stage renal disease after treatment with 90Y-DOTATOC. 1200 21

During fasting, a lack of GH increases protein loss by close to 50%, but the underlying mechanisms remain uncertain. The present study tests the hypothesis that the anabolic actions of GH depend on mobilization of lipids. Seven normal subjects were examined on four occasions during a 37-h fast with infusion of somatostatin, insulin, and glucagon for the final 15 h: 1) with GH replacement, 2) with GH replacement and antilipolysis with acipimox, 3) without GH and with antilipolysis, and 4) with GH replacement, antilipolysis, and infusion of intralipid. Urinary urea excretion, serum urea concentrations, and muscle protein breakdown (assessed by labeled phenylalanine) increased by almost 50% during fasting with suppression of lipolysis. Addition of GH during fasting with antilipolysis did not influence indexes of protein degradation, whereas restoration of high FFA levels regenerated proportionally low concentrations of urea and decreased whole body protein degradation (phenylalanine to tyrosine conversion) by 10-15%, but failed to affect muscle protein metabolism. Thus, the present data provide strong evidence that FFA are important protein-sparing agents during fasting. The finding that inhibition of lipolysis eliminates the ability of GH to restrict fasting protein loss indicates that stimulation of lipolysis is the principal protein-conserving mechanism of GH.
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PMID:The decisive role of free fatty acids for protein conservation during fasting in humans with and without growth hormone. 1297 Mar 12

Acutely increased intra-abdominal pressure (IAP) may lead to abdominal compartment syndrome (ACS), which ischaemia/reperfusion (I/R) injury plays an important role. The main goal of the management of ACS is to lower the intra-abdominal pressure despite reperfusion injury. Octreotide (OCT), a synthetic somatostatin analogue, lowers the splanchnic perfusion. The aim of this study was to investigate whether OCT improves the reperfusion injury after decompression of acute abdominal hypertension.Under anesthesia, a catheter was inserted intraperitoneally and using an aneroid manometer connected to the catheter, IAP was kept at 20 mmHg (ischemia group; I) for 1h. In the I/R group, pressure applied for an hour was decompressed and 1h reperfusion period was allowed. In another group of I/R, OCT was administered (50 microg/kg i.p.) immediately before the decompression of IAP. The results demonstrate that kidney and lung tissues of malondialdehyde (MDA; an end product of lipid peroxidation) levels and myeloperoxidase (MPO; index of tissue neutrophil infiltration) activity were elevated, while glutathione (GSH; a key to antioxidant) levels were reduced in I/R group (P<0.001). Moreover, OCT treatment applied in the I/R group reduced the elevations in blood urea nitrogen (BUN) and serum creatinine levels. Our results implicate that IAP causes oxidative organ damage and OCT, by reducing splanchnic perfusion and controlling the reperfusion of abdominal organs, could improve the reperfusion-induced oxidative damage. Therefore, its therapeutic role as a "reperfusion injury-limiting" agent must be further elucidated in IAP-induced abdominal organ injury.
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PMID:Octreotide: a new approach to the management of acute abdominal hypertension. 1470 53

Endocrine pancreas of zebrafish consist of at least four different cell types that function similarly to mammalian pancreatic islet. No mutants specifically affecting formation of the endocrine pancreas have been identified during the previous large-scale mutagenesis screens in zebrafish due to invisibility of a pancreatic islet. We combined in situ hybridization method to visualize pancreatic islet with an ethyl-nitroso-urea mutagenesis screen to identify novel genes involved in pancreatic islet formation in zebrafish. We screened 900 genomes and identified 11 mutations belonging to nine different complementation groups. These mutants fall into three major phenotypic classes displaying severely reduced insulin expression, reduced insulin expression with abnormal islet morphology, or abnormal islet morphology with relatively normal number of insulin expressing cells. Seven of these mutants do not have any other visible phenotypes associated. These mutations affect different processes in pancreatic islet development. Additional analysis on glucagon and somatostatin cell specification revealed that somatostatin cells are specified at a separate domain from insulin cells whereas glucagon cells are specified adjacent to insulin cells. Furthermore, glucagon cells and somatostatin cells are always associated with insulin cells in mutants that have scattered insulin expression. These data indicate that there are separate mechanisms regulating endocrine cell migration, proliferation, and differentiation. Further study on these mutants will reveal important information on novel genes involved in pancreatic islet cell specification and morphogenesis.
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PMID:Genetic analysis of early endocrine pancreas formation in zebrafish. 1609 13

The relation between xylitol concentration (1.0 and 5.5 mmol/1), the Capacity of Urea-N Synthesis, and the rate of Alanine Metabolism was investigated in nephrectomized rats of 200 g and compared with the effect of glucose at concentrations between 5.5 and 15.5 mmol/1. The xylitol and glucose concentrations were controlled by "clamp" techniques and the endogenous hormonal effects by somatostatin. The Capacity of Urea-N Synthesis was determined during alanine infusion to constant amino acid concentrations within the interval 7.3-11.6 mmol/1. The rate of alanine metabolism was assessed as alanine infusion rate corrected for changes in alanine concentration. At normal hormonal response, xylitol at 1.0 mmol/1 and 5.5 mmol/1 reduced urea synthesis from 10.3 +/- 1.1 mumol/(min.100 g) in controls to on average 6.2 +/- 0.9 mumol/(min.100 g) (mean +/- SD, n = 2 x 10, p < 1.01). Alanine metabolism was reduced to the same extent. Glucose concentration increased from 5.4 +/- 1.0 mmol/1 in controls to 8.1 +/- 1.4 mmol/1 at both xylitol concentrations. Xylitol reduced plasma glucagon concentration to one third and tripled plasma insulin concentration. During somatostatin and blood glucose maintained above 8 mmol/1, the Capacity of Urea-N Synthesis fell to 6.1 +/- 1.0 mumol/(min.100 g). In that situation, xylitol at 1.0 mmol/1 reduced neither urea synthesis nor alanine metabolism, whereas xylitol at 5.5 mmol/1 further reduced urea synthesis to 3.4 +/- mumol/(min.100 g) (n = 10, p < 0.05) and almost stopped alanine metabolism. Thus xylitol, independently of glucose and hormonal responses, inhibited urea synthesis and alanine metabolism. This may have therapeutic implications at catabolic conditions.
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PMID:Effects of xylitol versus glucose on urea synthesis and alanine metabolism in rats. 1683 75

The aim was to investigate the effect of lanreotide (Angiopeptin) on urea synthesis. Lanreotide is a somatostatin analogue used in therapy trials of certain cancers. Cancer patients are often protein catabolic, thus the effect of lanreotide on whole body protein metabolism is of importance. We investigated the effect of lanreotide by measuring urea nitrogen synthesis rate (UNSR) and blood alpha-amino nitrogen levels before, during and after a 30 min iv infusion of 25 g of an electrolyte-free amino acid solution. 6 healthy male subjects were studied following, i) placebo (saline), ii) lanreotide 5 mug/kg, and iii) lanreotide 80 mug/kg. Lanreotide decreased urea nitrogen synthesis rate (mmol/h) during amino acid infusion significantly compared to saline, independent of dose of lanreotide (max +/- SE of urea nitrogen synthesis rate measurements in each study: 117 +/- 8 mmol/h (saline), 85 +/- 10 mmol/h (high dose) and 85 +/- 12 mmol/h (low dose)). This occurred in spite of significantly higher plasma alpha-amino nitrogen following lanreotide (peak +/- SE of alpha-amino nitrogen level in each study: 3.7 +/- 0.1 mmol/l placebo versus 4.8 +/- 0.2 mmol/l low dose and 4.7 +/- 0.4 mmol/l high dose (p < 0.01). We conclude that a single dose of lanreotide decreases whole body urea nitrogen synthesis rate thereby conserving body protein. The results indicate that long term lanreotide therapy may not lead to further protein catabolism in cancer patients.
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PMID:Effect of lanreotide, a somatostatin analogue, on urea synthesis in normal man. 1684 68

We studied the effect of fructose on hepatic conversion of amino-N to urea-N as quantified by the Capacity of Urea-N Synthesis (CUNS) determined in rats during alanine loading. There were 2 control groups, one without and one with infusion of somatostatin, in order to control the effects of insulin and glucagon. Somatostatin reduced CUNS from 8.5 +/- 0.5 mumol/(min x 100 g BW) to 6.3 +/- 0.3 mumol/(min x 100 g BW) (mean +/- SEM) (p < 0.01) and reduced glucagon concentrations by 75% (p<0.05). Insulin and glucose concentrations did not change. Fructose, at blood concentrations of about 1 mmol/l further reduced CUNS to 3.6 +/- 0.3 mumol/(min x 100 g BW) (p < 0.01). Insulin increased slightly (p < 0.05), but neither glucose nor glucagon changed. At increasing fructose concentrations up to 2 mmol/l there was no further effect on CUNS. Fructose in concentrations as used for parenteral nutrition and independent of glucoregulatory hormones, decreased hepatic amino acid catabolism.
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PMID:Effect of fructose on the capacity of urea-N synthesis in rats. 1684 92


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