Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As the long-acting somatostatin analog octreotide attenuates polypeptide hormone hypersecretion, it has recently been used to effectively treat acromegaly and gastrointestinal carcinoid tumors. Most growth-promoting actions of GH are mediated by insulin-like growth factor-I (IGF-I), which circulates complexed with multiple binding proteins (IGFBPs). IGFBP-1, a nonglycosylated peptide, competes with the IGF-I receptor for ligand binding and also regulates IGF action. To examine GH-independent mechanisms for octreotide regulation of the GH axis, circulating levels of IGFBP-1 were measured hourly after sc octreotide or saline administration in normal and GH-deficient adults. As IGFBP-1 is inhibited by insulin and GH, the dynamic pattern of alterations in GH and insulin levels was also assessed. After octreotide (100 micrograms) administration to 10 normal subjects, mean IGFBP-1 concentrations were stimulated from 23 +/- 4 to 72 +/- 18 micrograms/L (P < 0.007 vs. saline) after 2 h. Maximal induction of IGFBP-1 levels occurred after 3 h (325 +/- 115 micrograms/L; P < 0.02 vs. saline) and remained elevated (P < 0.005) for 6 h. IGFBP-1 was induced by octreotide in all subjects and was confirmed by Western ligand blotting. Insulin and GH levels preceding the rise in IGFBP-1 were unaltered by octreotide. Octreotide stimulated IGFBP-1 5-fold during a sustained fast in 4 normal subjects, despite equally suppressed insulin levels in both saline- and octreotide-treated groups. In 4 GH-deficient adults, IGFBP-1 levels were stimulated by octreotide from 16 +/- 3 to 146 +/- 36 and 154 +/- 28 micrograms/L after 3 and 4 h, respectively. In conclusion, the somatostatin analog octreotide induces IGFBP-1 independently of GH and insulin. As IGFBP-1 regulates the action of IGF-I, octreotide stimulation of IGFBPs may represent an additional pharmacological mechanism for attenuating the GH-IGF-I axis.
 ...
PMID:Octreotide stimulates insulin-like growth factor-binding protein-1: a potential pituitary-independent mechanism for drug action. 128 85

Effects of growth hormone-releasing factor (GRF) and intake on arterial concentrations and net visceral metabolism of hormones were measured in six growing Hereford x Angus steers using a split-plot design with 4-wk injection periods within 8-wk intake periods. Steers were fed a 75% concentrate diet at two intakes and were injected s.c. twice daily with saline or GRF (10 micrograms/kg of BW). Arterial concentrations of growth hormone (GH) were measured on d 1 and d 8 to 10 of injections. Eleven measurements, obtained at 30-min intervals, of arterial concentration and net flux of hormones across portal-drained viscera (PDV) and liver were obtained on d 8 to 10 of injections (six hourly measurements were used for insulin-like growth factor-I [IGF-I] and somatostatin). The area under the GH curve and average and peak GH concentrations were increased (P less than .01) by GRF and were greater (P less than .10) at low than at high intake. Liver removal of GH was not affected by GRF or intake. Arterial IGF-I concentration was increased (P less than .05) by GRF and not affected by intake. Treatments did not affect IGF-I flux across the liver. Arterial insulin concentration was greater (P less than .05) at high than at low intake, in part because of greater (P less than .01) PDV release. Increased (P less than .10) arterial insulin concentration in GRF-treated steers was not attributable to significant changes in PDV or liver net flux. Arterial glucagon concentration was greater (P less than .01) at high than at low intake, in part because of greater (P less than .05) PDV glucagon release and decreased (P less than .10) liver extraction ratio. Effects of intake on arterial concentration of insulin and glucagon were in part due to changes in visceral metabolism, but GRF did not affect PDV or liver hormone metabolism.
 ...
PMID:Effects of growth hormone-releasing factor and feed intake on energy metabolism in growing beef steers: net hormone metabolism by portal-drained viscera and liver. 134 45

Ethanol administration decreases GH secretion in humans and experimental animals. The mechanism of these inhibitory effects was investigated by evaluating the spontaneous secretory pattern of GH in chronically cannulated unanesthetized rats, plasma insulin-like growth factor-I (IGF-I) concentrations, and hypothalamic GH-releasing hormone (GHRH) and somatostatin, and pituitary GH mRNA levels. Body weight gain was reduced in ethanol (5%)-liquid diet-fed rats (n = 6) for 6 days compared to that in both isocalorically pair-fed controls (n = 6) and ad libitum-fed animals (n = 6). Spontaneous GH secretion was markedly decreased (by 75-90%) in ethanol-fed rats compared to that in pair-fed and ad libitum-fed groups, while pulsatile pattern of GH release was preserved, with secretory bursts occurring every 180-220 min in all groups. Mean 6-h plasma GH levels in ethanol-, pair-, and ad libitum-fed animals were: 18.8 +/- 4.5, 113.3 +/- 14.9, and 179.6 +/- 30.1 ng/ml, respectively (P < 0.01, ethanol vs. each control). Plasma IGF-I concentrations were decreased in the ethanol-fed rats (338 +/- 16 ng/ml) compared to those in pair-fed (427 +/- 39 ng/ml; P < 0.05) and ad libitum-fed (769 +/- 25 ng/ml; P < 0.01) rats. Ethanol treatment decreased GHRH mRNA levels to 9% of those in ad libitum-fed (P < 0.01) and 20% of those in pair-fed (P < 0.05) animals, whereas it did not significantly alter somatostatin or GH mRNA levels. The results indicate that the effects of ethanol inhibit GH secretion primarily at the hypothalamic level, resulting in impaired GHRH gene expression. Since the GHRH-GH-IGF-I axis has an important role in growth regulation, the growth retardation seen in experimental models of alcohol abuse may be a consequence at least in part of the suppressive effects of ethanol on this axis.
 ...
PMID:Inhibitory effects of ethanol on the growth hormone (GH)-releasing hormone-GH-insulin-like growth factor-I axis in the rat. 135 62

Diabetes mellitus was induced using streptozotocin in five gilts between 8 and 12 weeks of age. Gilts were maintained with exogenous insulin (INS) except during experimental periods. Four litter-mate gilts served as controls. At 9 months of age, all gilts were ovariectomized, and 30 days after ovariectomy, Experiment (Exp) 1 was conducted. Jugular vein catheters were inserted and blood samples were collected every 10 min for 8 hr. Experiment 2 was conducted when gilts were 11 months of age. Venous blood and cerebrospinal fluid (CSF) samples were collected in the absence (Phase I) or presence (Phase II) of INS therapy. In Experiment 1, plasma glucose concentrations were greater (P < 0.05) in diabetic (465 +/- 17 mg/100 ml) than in control (82 mg +/- 17 mg/100 ml) gilts, whereas serum INS was lower (P < 0.0001) in diabetic gilts (0.3 +/- 0.02 vs 0.9 +/- 0.05 ng/ml) and insulin-like growth factor-I was similar in diabetic and control gilts (32 +/- 3 vs 43 +/- 4 ng/ml, respectively). Mean serum GH concentration was 2-fold greater (P < 0.02) in diabetics (2.8 +/- 0.4 ng/ml) than in control gilts (1.2 +/- 0.2 ng/ml). Diabetic gilts exhibited a greater (P < 0.05) number of GH pulses than control gilts (3.2 +/- 0.4 vs 1.5 +/- 0.3/8 hr, respectively). In addition, GH pulse magnitude was markedly elevated (P < 0.02) in diabetic (5.8 +/- 0.4 ng/ml) compared with control gilts (3.3 +/- 0.6 ng/ml). Mean basal serum GH concentrations were greater (P < 0.07) in diabetic (2.2 +/- 0.5 ng/ml) compared with control gilts (1.0 +/- .1 ng/ml). In Experiment 2, CSF concentrations of insulin-like growth factor-I, INS, GH, and protein were similar for diabetic and control gilts in both phases. Serum GH levels were similar for diabetics and controls in Phase I, but were greater (P < 0.05) in diabetics than in controls in Phase II. CSF glucose levels were greater in diabetic than in control gilts in both the presence (P < 0.003) and absence (P < 0.0002) of INS therapy, whereas plasma glucose was greater (P < 0.003) in diabetic than in control gilts in the absence of INS, but returned to control concentrations in the presence of INS. However, serum GH levels were unchanged after INS therapy in the diabetic gilts. In conclusion, altered GH secretion in the diabetic gilt may, in part, be due to elevated CSF glucose concentrations, which may alter GH-releasing hormone and/or somatostatin secretion from the hypothalamus.
 ...
PMID:Growth hormone secretion, serum, and cerebral spinal fluid insulin and insulin-like growth factor-I concentrations in pigs with streptozotocin-induced diabetes mellitus. 140 37

The in vivo effects of recombinant human insulin-like growth factor-I (rhIGF-I) on whole body protein metabolism were studied to ascertain whether rhIGF-I has comparable effects as those reported with rhGH use in humans. The doses of rhIGF-I chosen achieved similar plasma IGF-I concentrations as those achieved after 7 days of rhGH injections. Eight normal volunteers were studied using [1-13C]- and [1-14C]leucine tracers, before, 4 h, and 28 h after a continuous infusion of rhIGF-I at 5 micrograms kg-1 h-1 (n = 6) and 10 micrograms kg-1 h-1 (n = 2). Two additional subjects were studied in a protein catabolic state after 7 days of high dose (0.8 mg kg-1 day-1) glucocorticosteroid administration. Plasma concentrations of rhIGF-I were similar using either 5 or 10 micrograms kg-1 h-1 and increased to values approximately 300% above baseline by 28 h of infusion. No decrease in the plasma glucose concentration was observed during the 28-h infusion; however, plasma insulin, C-peptide, and glucagon concentrations significantly decreased, whereas plasma free fatty acids were not affected. No changes were observed in the rate of proteolysis (as estimated by the rate of leucine appearance), the rate of leucine oxidation, or the rate of protein synthesis in the absence or presence of glucocorticosteroid treatment. Plasma concentrations of insulin-like growth factor binding protein-3 did not change during the rhIGF-I infusion whereas they increased 50% in subjects who received rhGH, and in whom rhGH caused a potent protein anabolic effect. These results suggest that rhIGF-I may have a somatostatin-like effect. In addition, we found that rhIGF-I infusion is insufficient to promote protein anabolism. This may be due to the failure of rhIGF-I alone to induce a pivotal GH-dependent cofactor(s) necessary for IGF-I to elicit an anabolic effect on protein metabolism in humans.
 ...
PMID:Low dose recombinant human insulin-like growth factor-I fails to affect protein anabolism but inhibits islet cell secretion in humans. 143 76

Although premature infants have high umbilical cord GH levels, little is known about spontaneous GH release in these individuals. The purpose of our study was to investigate spontaneous 12-h GH release in appropriate for gestational age male and female premature infants. We studied 22 premature infants (15 males and 7 females) of appropriate length and weight for age. Gestational ages, birth weights, birth lengths, and ages at the time of study were similar in male or female infants. All infants were biochemically euthyroid. Blood was taken every 30 min over a 12-h period from an indwelling umbilical catheter; no stress occurred during the blood withdrawal. GH was determined by a double antibody RIA, using 0.01 mL plasma. GH pulse detection was undertaken using Cluster, a computerized pulse detection algorithm. Total insulin-like growth factor-I and -II (IGF-I and -II) levels were measured after separation of the IGFs from the serum binding proteins. Spontaneous pulsatile GH release was observed in all infants studied. No differences were found between males and females in the pulse characteristics of frequency, maximal amplitude, incremental amplitude, width, or area. The GH pulse frequency per 12 h was 3.2 +/- 0.3 (mean +/- SE) in males and 3.0 +/- 0.7 in females. The maximal pulse amplitude was 50.7 +/- 6.2 micrograms/L in males and 44.7 +/- 9.0 micrograms/L in females. The incremental pulse amplitude was 24.3 +/- 3.2 micrograms/L in males and 20.2 +/- 3.9 micrograms/L in females. The mean 12-h GH level was 37.1 +/- 4.8 micrograms/L in males and 35.8 +/- 8.5 micrograms/L in females; the average GH nadir was 26.1 +/- 4.0 micrograms/L in males and 24.4 +/- 8.3 micrograms/L in females. Both IGF-I and IGF-II concentrations were similar in males and females. The mean IGF-I levels were 10.7 +/- 1.5 ng/mL in males and 7.5 +/- 1.1 ng/mL in females; IGF-II levels were 96.0 +/- 12.0 ng/mL in males and 115.4 +/- 17.1 ng/mL in females. These results demonstrate similar pulsatile GH release in male and female premature infants at a mean age of 32-33 weeks. Compared with previously reported values for mean GH concentration and average GH nadir in older children, the values in these premature infants were much higher. We speculate that the higher GH levels in premature infants may result from decreased negative feedback associated with low IGF-I levels. The premature infant's somatotrophs may also not fully respond to the GH inhibitory action of somatostatin.
 ...
PMID:Spontaneous pulsatile growth hormone release in male and female premature infants. 146 56

In acromegaly, GH hypersecretion occurs despite elevated insulin-like growth factor-I (IGF-I) levels, implying defective IGF-I feedback. To study the possible mechanisms of defective IGF-I negative feedback in acromegaly, we assessed parameters of pulsatile GH secretion during fasting-induced decrease in plasma IGF-I. Seven patients with active acromegaly and six normal controls were fasted for 6 days and GH secretory profiles were obtained by frequent (every 10 min) blood sampling for 24 h and analyzed by Cluster. Fasting resulted in similar decreases in IGF-I, body weight, and blood glucose levels, and increases in free fatty acid and beta-hydroxybutyrate in all subjects. Normal subjects showed increases in 24-h total and pulsatile GH production, GH pulse frequency, maximal pulse amplitude, interpulse and nadir levels, implying suppression of hypothalamic somatostatin secretion and increase in GH-releasing hormone (GHRH) pulse frequency. In acromegalic patients, GH (and, by inference, GHRH) pulse frequency was unchanged. Three patients had increases in GH production, interpulse, and nadir levels similar to the normals while the other four had no change or paradoxical decreases in these parameters. Percentage change in GH production was highly correlated with percentage change in interpulse and nadir levels in both normals and patients. Mean GH response to GHRH (0.33 micrograms/kg iv) did not change significantly in any group as a result of fasting. Our data suggest that in healthy humans IGF-I negative feedback on GH secretion involves suppression of GHRH pulse frequency. GH (and, by inference, GHRH) pulse frequency is resistant to decrease in IGF-I in acromegaly, suggesting that lowered sensitivity of GHRH neurons to IGF-I may be the mechanism of high GH pulse frequency in this disease.
 ...
PMID:Regulation of pulsatile growth hormone secretion by fasting in normal subjects and patients with acromegaly. 151 71

Acromegaly is characterized by growth hormone (GH) hypersecretion and insulin-like growth factor-I (IGF-I) excess, both of which stimulate osteoblast proliferation. At diagnosis, GH excess has usually been present for years. Furthermore, impaired gonadotropin secretion with hypogonadism is frequent. To date, studies of changes in bone mineral density (BMD) in acromegaly have been limited and the available data inconsistent. To investigate the effects of GH excess on proximal femur and lumbar spine BMD, a case series of 25 patients with acromegaly (8 eugonadal, 17 hypogonadal) documented by high plasma GH and IGF-I concentrations was studied. BMD was measured using dual-photon absorptiometry, hormonal and biochemical measurements, which included GH, IGF-I, serum calcium, phosphate, alkaline phosphatase, 1,25 dihydroxy vitamin D and urinary calcium and hydroxyproline excretion. Seven patients were re-studied after IGF-I was suppressed for six months by the somatostatin analog 201-995 (five patients) or pituitary adenomectomy (two patients). BMD was normal in 22 patients and was decreased at one site each in one eugonadal and two hypogonadal patients. BMD was similar between the eugonadal and hypogonadal groups at all sites. Urinary hydroxyproline excretion was equally increased in both groups. There was no correlation between any of the hormonal or biochemical parameters and the age, sex, race and body mass index matched Z-scores of BMD at any site. Following normalization of IGF-I for 6 mo in seven patients, there was no significant change of BMD. We conclude that proximal femoral and lumbar spine BMD is normal in most patients with active acromegaly, including those who are hypogonad. Successful treatment of acromegaly does not result in major short-term changes in BMD.
 ...
PMID:Bone mineral density of the axial skeleton in acromegaly. 151 33

We have detected somatostatin receptors (SSR) by autoradiography in 3/4 established small cell lung cancer (SCLC) cell lines but not in two non-SCLC cell lines. The growth of 1/3 SSR positive SCLC cell lines was significantly inhibited by the long-acting somatostatin analogue octreotide (SMS 201-995, Sandostatin) 10(-9) M. We treated 20 SCLC patients with octreotide 250 micrograms three times daily for 1 week prechemotherapy (six patients) or at relapse after chemotherapy (14). Octreotide was well tolerated, and serum insulin-like growth factor-I levels were suppressed to 62 +/- 7% of pre-treatment levels. However there was no evidence of anti-tumour activity measured by tumour bulk or serum levels of neuron-specific enolase. In one patient metastatic skin nodules were shown to be SSR positive before and at the end of 2 weeks octreotide. Despite this the patient had progressive disease, and tumour cells obtained by fine needle aspirate before and after treatment showed no growth inhibition when cultured with octreotide immediately or following establishment as a cell line. In summary we saw little correlation between SSR expression and growth inhibition by octreotide, either in vitro or clinically.
 ...
PMID:Experimental and clinical studies with somatostatin analogue octreotide in small cell lung cancer. 165 81

The effects of GH, PRL, and placental lactogen (PL) on the proliferation of pancreatic beta-cells in vitro were studied as well as the possible effect of insulin-like growth factor-I (IGF-I) in mediating this effect. Proliferating beta-cells were identified by staining with a monoclonal antibody to bromodeoxyuridine (BrdU) after cells were incubated for 1 h in the presence of 10 microM BrdU. By double staining with insulin antibodies it was found that 6.3% of the beta-cells had incorporated BrdU when cultured for 7 days in the presence of 1 microgram/ml human GH (hGH) compared to 0.6% when cultured in the absence of hGH. Similar results were obtained using rat GH. The half-maximal effect of hGH on beta-cell proliferation was observed at 10 ng/ml, and the maximal effect at 100 ng/ml. Islet cells cultured in the presence of PRL or PL caused a dose-dependent increase in beta-cell proliferation similar to that caused by hGH. GH, PRL, and PL had no effect on the proliferation of glucagon- or somatostatin-producing cells. The addition of 100 ng/ml IGF-I to either control or GH-stimulated islet cells did not affect the labeling index. When GH-stimulated proliferation of beta-cells was measured in the presence of neutralizing concentrations of a rabbit IGF-I antiserum, the percentage of beta-cells incorporating BrdU was unaffected. Using Northern blot analysis, no IGF-I transcripts could be detected in RNA from GH-stimulated islets, whereas IGF-I transcripts were readily detected in RNA isolated from rat liver tissue. These data suggest that the stimulatory effect of GH, PRL, and PL on beta-cell proliferation is not mediated by IGF-I, but, rather, is a direct mitogenic effect on the beta-cell.
 ...
PMID:The stimulatory effect of growth hormone, prolactin, and placental lactogen on beta-cell proliferation is not mediated by insulin-like growth factor-I. 167 31


1 2 3 4 5 6 7 8 9 10 Next >>