Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 insulin-like growth factors (IGFs) exist primarily bound to cell surface receptors or complexed to specific binding proteins (IGFBPs). The IGFBPs modulate the bioavailability of the IGFs and may enhance or inhibit IGF actions. Several distinct forms of IGFBPs have been described on the basis of size, immunological determinants, and distribution in biological fluids; the IGFBPs may differ as well in their biological function. Sheep thyroid cells produce IGFBPs under hormonal regulation. Cells grown in basal medium or with six-hormone (6H) medium supplements (transferrin, glycyl-histidyl-lysine, hydrocortisone, somatostatin, insulin, and TSH) release nonglycosylated BPs that migrate at 24, 27, 29, and 32 kDa on Western ligand blot. Cells cultured with the thyroid mitogens epidermal growth factor and phorbol ester release additional glycosylated IGFBPs of 40-44 kDa. Immunoprecipitation experiments indicate that 29- and 32-kDa IGFBPs are antigenically related to IGFBP-2, and the 40- to 44-kDa proteins are related to IGFBP-3. Using specific cDNA probes IGFBP-1, -2, and -3, we examined the regulation of IGFBP mRNA levels in sheep thyroid cultures. The rat IGFBP-2 cDNA probe hybridized to an approximately 1.6-kilobase mRNA species in cells under all culture conditions. However, IGFBP-3 mRNA was detectable only in epidermal growth factor- or phorbol ester-treated cells and appeared within 4 h, preceding the release of IGFBP-3 protein into the medium. The 6H additives, which stimulate differentiated function in thyroid cells, inhibited the mRNA levels of both IGFBP-2 and IGFBP-3. IGFBP-1 mRNA was not detectable. The distinct regulation of these IGFBPs suggest that they may play different biological roles in modulating thyroid physiology.
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PMID:Regulation of insulin-like growth factor-binding protein messenger ribonucleic acid levels in sheep thyroid cells. 170 62

Isolated sheep thyroid follicles release specific insulin-like growth factor-binding proteins (IGFBPs). Since IGFBPs can modulate IGF bioactivity, at least in vitro, their presence in thyroid tissue may influence synergistic interactions between TSH and endogenous IGF-I or -II which are known to control both thyroid growth and function. We have examined the hormonal control of IGFBP release in relation to iodine organification. Sheep thyroid follicles were isolated by incubation with collagenase and differential centrifugation, grown in Coon's modified Ham's F12M medium with the addition of transferrin, glycylhistidyl-lysine, somatostatin (3H), TSH, cortisol and insulin (6H), and maintained in OH (hormone-free) or 3H medium with or without further supplements for 48 h. Conditioned culture medium was separated by 8% sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis, transferred to nitrocellulose and incubated with 125I-labelled IGF-II followed by autoradiography (ligand blot). Additionally, the radioactive bands were cut from the filters and quantified by gamma-spectrometry. Iodine organification was assessed by incubation of follicles with 10(6) c.p.m. Na125I for 3 h before washing, solubilization in 0.1 mol NaOH/l and the precipitation of organified radioisotope with 10% (v/v) trichloroacetic acid. Cells conditioned in OH or 3H medium released specific IGFBPs of 46, 34, 28 and 19 kDa on ligand blot analysis. The proteins of 34 and 19 kDa were immunopositive on Western blot analysis using anti-bovine IGFBP-2 antiserum. The 46-kDa IGFBP was retained by Concanavalin A-Sepharose chromatography and demonstrated to be glycoprotein. This is probably ovine IGFBP-3. The addition of TSH, or TSH plus cortisol to OH or 3H medium significantly decreased the 125I-labelled IGF-II associated with the 34- and 28-kDa IGFBP species. All IGFBP species were substantially reduced in 6H medium, which was predominantly due to the effects of TSH and cortisol. When total 125I-labelled IGF-II associated with IGFBPs was considered, a significant (P less than 0.01) inverse correlation existed between IGFBP activity and iodine organification in the same cultures; the latter being greatest in OH or 3H medium supplemented with TSH and cortisol. None of these hormone additions altered the endogenous release of IGF-II by the cells. These results suggest that endogenous IGFs, under hormonal control, may modulate the action of endogenous IGF in the regulation of thyroid function.
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PMID:Hormonal regulation of insulin-like growth factor (IGF)-binding proteins secreted by isolated sheep thyroid epithelial cells: relationship with iodine organification. 171 78

We have recently shown that hypersomatostatinemia is a feature of cystic fibrosis (CF) when these patients have CF-associated pancreatogenic diabetes mellitus (CFDM). To address the possibility that patients with CFDM might have suppressed pituitary growth hormone (GH) release as a result of increased plasma somatostatin, GH secretion in 8 CFDM patients and 8 normal male controls was studied using a standard arginine infusion stimulus. Concentrations of the GH-dependent peptides, insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3) were also measured. We found that mean GH concentrations in the CFDM group were significantly increased (p < 0.05) rather than decreased at the 30-min (12.3 +/- 3.6 vs. 3.8 +/- 1.9 ng/ml), 45-min (15.4 +/- 2.9 vs. 6.1 +/- 2.3 ng/ml) and 60-min (13.2 +/- 2.3 vs. 6.2 +/- 2.2 ng/ml) time points of study. Mean GH area under the curve (633 +/- 128 vs. 249 +/- 107 ng/ml) was also significantly greater (p < 0.05) in the CFDM group. Despite higher GH levels in the CFDM patients, their IGF-I and IGFBP-3 concentrations were low. We conclude that plasma somatostatin elevations in the CFDM group are not of sufficient magnitude to suppress pituitary GH release. Decreased levels of growth mediating peptides in the relatively malnourished CF subjects suggest a pattern of malnutrition-induced GH resistance which may contribute to poor weight and height gain.
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PMID:Effect of hypersomatostatinemia on growth hormone secretion in cystic fibrosis patients with diabetes. 750 19

We describe a case of recurrent hypoglycaemia associated with a hepatoma. During hypoglycaemia serum insulin was undetectable. Plasma insulin-like growth factor II (IGF-II) was not elevated although 71% of plasma IGF-II was present as big IGF-II (molecular weight 11 kDa) which probably represents a non-glycated form of pro-IGF-II. The GH response to hypoglycaemia was impaired and plasma levels of both IGF-I and the GH-dependent IGF binding protein (IGFBP-3) were low. A recently described unextracted assay directed against the first 21 amino acids of the E-domain (E-21) of proinsulin-like growth factor-II (pro-IGF-II) allows direct plasma estimation (plasma E-21) of larger molecular forms of IGF-II without interference from normal IGF-II and IGF binding proteins. Basal values were grossly elevated (23.7 and 23.8 nmol/l). Treatment with GH led to an increase in the mean plasma glucose across 24 hours (4.25 +/- 0.21 mol/l (mean +/- SEM) before treatment, compared with 4.86 mmol/l +/- 0.17 following GH (P < 0.01)) and a reduction in hypoglycaemic attacks. The treatment was associated with a rise in IGFBP-3 and small increases in insulin like growth factors. Subsequent treatment with the somatostatin analogue octreotide did not produce a significant change in plasma glucose levels or insulin-like growth factors. Two courses of intrahepatic adriamycin restored elevated levels of E-21 to normal. Total IGF-II remained normal and IGF-I increased. GH treatment was successfully withdrawn with no effect on plasma glucose or growth factor levels. The patient remained free from hypoglycaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A case of hepatoma associated with hypoglycaemia and overproduction of IGF-II (E-21): beneficial effects of treatment with growth hormone and intrahepatic adriamycin. 752 21

Octreotide, a long-acting analog of somatostatin that inhibits insulin release, has the potential to control hypoglycemia in infants with congenital hyperinsulinism. To examine the efficacy and side effects of octreotide, we evaluated therapy between 1988 and 1993 in 16 infants who did not respond to diazoxide. In nine patients with onset of severe hypoglycemia in the first days of life, octreotide was helpful in stabilizing plasma glucose levels and allowed reductions in the rates of glucose infusion; however, glucose control was inadequate to avoid subtotal pancreatectomy. In two of these nine patients postoperatively and in seven other infants, a trial of long-term treatment with octreotide was undertaken. Four were treated successfully for up to 4.3 years. Octreotide therapy was not associated with thyroid deficiency and caused only transient malabsorption. All patients receiving long-term therapy had some decrease in linear growth and two had subnormal plasma concentrations of insulin-like growth factor I and insulin-like growth factor binding protein 3 compatible with suppression of growth hormone by octreotide. Resistance to octreotide therapy, even with increasing doses, occurred in all patients. These results suggest that octreotide may aid in the acute or long-term treatment of congenital hyperinsulinism in a limited number of selected cases.
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PMID:Short- and long-term use of octreotide in the treatment of congenital hyperinsulinism. 841 May 9

It has recently been demonstrated in various clinical experiments that native somatostatin and its long-acting analogues increase circulating levels of insulin-like growth factor-binding protein-1 (IGFBP-1) within 1-2 h, independent of effects on circulating insulin or glucose levels. Using human hepatoma cells in vitro the somatostatin analogue, octreotide, has been shown to increase IGFBP-1 mRNA within 24 h indicative of a direct stimulatory effect of octreotide on IGFBP-1 synthesis. In order to ascertain whether octreotide acutely stimulates IGFBP-1 mRNA in vivo, placebo or two doses of octreotide were injected subcutaneously into three groups of rats. One hour after saline or octreotide administration, liver, kidney and serum were obtained for the measurement of IGFBPs-1 to -6 mRNA in tissue and IGFBPs and IGF-I in serum. Octreotide increased liver IGFBP-1 (562%) and IGFBP-3 (23%) mRNA expression with a concomitant rise in the circulating 30 kDa (106%) and 38-42 kDa (23%) IGFBPs. No detectable changes were seen in other liver IGFBP transcripts, other circulating IGFBPs or in any of the kidney IGFBP transcripts. Serum IGF-I increased by 37% in the animals receiving the high octreotide dose. No concomitant changes were observed in glucose or insulin levels. These data show that octreotide acutely stimulates hepatic IGFBP-1 and -3 mRNA in vivo in rats. The stimulating effect on IGFBP-3 presents a possible hitherto unknown form of regulation of IGFBP-3 whilst the effect on IGFBP-1 indicates that the stimulatory effect of octreotide on circulating IGFBP-1 described in clinical trials may be due to increased hepatic production. The present findings may be of importance in the clinical use of octreotide.
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PMID:Stimulation of hepatic insulin-like growth factor-binding protein-1 and -3 gene expression by octreotide in rats. 854 25

Hyperinsulinemic euglycemic clamps were performed on six patients with compensated alcoholic cirrhosis and on six normal comparison subjects. As in previous studies, glucose uptake in the cirrhotic patients was only 21% of the comparison value. The cirrhotic patients had high growth hormone (GH) and low insulin-like growth factor-I (IGF-I) levels, with low insulin-like growth factor-binding protein (IGFBP)-3 levels, but surprisingly high IGFBP-I levels (26.8 +/- 8.4 microgH vs. 3.2 +/- 0.2 microm/L, P < .001). The log IGFBP-1 level was inversely correlated with the log insulin sensitivity (r = -.95). The clamps were repeated with a somatostatin infusion to suppress GH secretion. IGFBP-1 increased in both groups, especially in the cirrhotic subjects. Insulin sensitivity increased in the normal subjects but was unchanged in the cirrhotic patients. Following GH treatment (0.13 U/kg/d for 5 days), the clamps were repeated. GH, IGF-1, and IGFBP-3 levels were now similar in the two groups; IGFBP-1 levels decreased in the cirrhotic patients but remained fivefold higher than the comparison value (10.6 +/- 3.7 vs. 2.1 +/- 0.4, P < .05). Glucose uptake in the cirrhotic patients remained only 29% of the comparison value, but the change in their insulin sensitivity was inversely correlated with the change in their IGFB-1 levels (r = -.84). These results suggests an important role for IGFBP-1 in modulating insulin sensitivity in cirrhosis.
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PMID:High insulin-like growth factor binding protein 1 levels in cirrhosis: link with insulin resistance. 870 51

In normal subjects, the major form of circulating IGF is the GH-dependent 150 K complex. As demonstrated by gel-permeation chromatography, the acid-labile subunit (ALS) purified from human serum, incubated for 2 h at 20 degrees C with [125I]IGF-I and rIGFBP-3, is able to increase not only the molecular weight (mol. wt.) of the IGF-IGFBP-3 complex, but also the amount of IGF-I bound. In both charcoal and polyethylene glycol ligand binding assays, competitive binding curves for the displacement of [125I]IGF-I from rIGFBP-3 by increasing concentrations of unlabeled IGF-I showed an increased binding activity of rIGFBP-3 in the presence of ALS. The effect of ALS on rIGFBP-3 binding activity was dose dependent. In addition, ligand and immunoblot revealed that ALS and rIGFBP-3 are able to form a high mol. wt. complex in the absence of IGF peptide. On the basis of these data, ALS seems to have a more complex function than that of simply increasing the mol. wt of the IGF-IGFBP-3 complex. The regulation of ALS synthesis by rat hepatocytes in primary culture has also been evaluated by immunoblot. In agreement with the in vivo finding of an inhibitory effect of octreotide (a somatostatin analog) on the formation of the 150 K complex in acromegalic subjects, we could observe in vitro that octreotide produces a dose-dependent inhibition of ALS secretion into the hepatocyte conditioned medium. TGF-beta 1 was also inhibitory at high doses. On the contrary, we could not evidence any effect of IGF-I or IGF-II, while a small increase has been noted after incubation with T3.
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PMID:Functions and regulation of the acid-labile subunit of the 150 K complex. 881 66

Octreotide nasal powder is a delivery system of the somatostatin analogue developed to overcome the inconvenience of repeated subcutaneous administrations. Eight patients with clinically active acromegaly were treated for three months with octreotide nasal powder which was administered at the initial dosage of 0.125 mg tid, doubling the dosage up to 2 mg tid in order to obtain a mean GH value below 5 micrograms/l during 8 daytime hours. In 4 of these patients, treatment was prolonged till the sixth month. Blood samples were taken on days 15, 29, 43, 55, 90, 120, 150, 180 for GH, IGF-I, IGFBP-3, IGFBP-1 and insulin measurements. Before treatment, mean daytime GH and morning IGF-I serum levels were both increased but not correlated with each other. Serum IGFBP-3 levels were higher than normal and positively correlated with those of GH, IGF-I and insulin. Insulin levels were elevated and positively correlated with those of GH but not with those of IGF-I and IGFBP-1. Serum IGFBP-1 levels were in the low normal range and not correlated with any of the other parameters. Treatment with octreotide nasal powder induced in all patients a marked decrease of GH which lowered below 5 micrograms/l in 7/8 patients and IGF-I levels, which fell within the normal range in 1 patient. Serum IGFBP-3 and insulin concentrations decreased by 26% and 71%, respectively, and those of IGFBP-1 underwent an only transient increase in 5/8 patients. Opposite changes of insulin and IGFBP-1 levels, with a decrease of the former followed by an increase of the latter were noted during the 8 hours following an octreotide nasal insufflation. During chronic octreotide treatment, positive correlations were found between GH and IGF-I, GH and IGFBP-3, IGF-I and IGFBP-3, insulin and IGFBP-3 and insulin and IGF-I. An improvement of the clinical picture was registered in all patients after a few days of octreotide nasal powder administration. Treatment was well tolerated, with only mild side effects and no significant changes in the nasal mucosa, and the patients' compliance was excellent.
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PMID:Effect of chronic treatment with octreotide nasal powder on serum levels of growth hormone, insulin-like growth factor I, insulin-like growth factor binding proteins 1 and 3 in acromegalic patients. 890 79

The early renal growth in streptozotocin (STZ)-induced diabetic rats is preceded by a transient rise in renal tissue insulin-like growth factor (IGF)-I concentration. Administration of the long-acting somatostatin analog octreotide to STZ diabetic rats inhibits the early increase in kidney IGF-I and the increase in kidney size without affecting metabolic control. We studied the effects of octreotide treatment on the intrarenal IGF axis at 2 and at 7 days after the induction of STZ diabetes. Two days after induction of diabetes, kidney IGF-I was increased from 850 +/- 43 ng/g tissue in controls to 1,648 +/- 165 ng/g tissue (P < 0.001) in diabetic animals. The diabetes-associated increase in renal IGF-I 48 h after STZ injection was totally prevented by octreotide (IGF = 780 +/- 57 ng/g tissue). However, 7 days after the induction of diabetes, kidney IGF-I was similar to that of control and was not affected by octreotide. No difference in serum IGF-I was observed between controls and diabetic rats after 2 days of diabetes; however, octreotide treatment resulted in a significant decrease of serum IGF-I after 2 days when compared with control rats (P < 0.05). Renal IGF-I mRNA was significantly decreased to the same extent in both diabetic groups 2 and 7 days after the induction of diabetes, while renal IGF-I receptor (IGF-IR) mRNA was unchanged in rats from either group. Two days after induction of diabetes, renal insulin-like growth factor binding protein (IGFBP)-1 mRNA and 30-kDa IGFBPs (containing IGFBP-1) increased by 186 and 192%, respectively, in untreated diabetic animals compared with controls. Octreotide treatment prevented the diabetes-associated rise in renal IGFBP-1 mRNA and protein. However, 7 days after the induction of diabetes, renal IGFBP-1 mRNA and protein were similarly increased in both octreotide-treated or untreated diabetic rats. Renal IGFBP-3 gene expression and protein and IGFPB-5 mRNA remained unchanged after 2 and 7 days of diabetes when treated or untreated with octreotide. We conclude that the well-known inhibitory effect of octreotide on the early increase in renal IGF-I concentration and renal size in diabetes may be mediated through a direct effect on renal IGFBP-1 levels.
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PMID:Octreotide prevents the early increase in renal insulin-like growth factor binding protein 1 in streptozotocin diabetic rats. 960 70


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