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)

Insulin is the principal regulator of hepatic insulin-like growth factor binding protein-1 (IGFBP-1) production, mediating the rapid decrease in plasma IGFBP-1 in response to nutritional intake. In this study, we defined IGFBP-1 regulation by insulin in upper and lower body obesity, conditions associated with insulin resistance and chronic hyperinsulinemia. Overnight postabsorptive IGFBP-1 levels in obese and nonobese women showed an inverse, nonlinear relationship with plasma insulin concentrations. Maximum suppression of IGFBP-1 was seen at 70-90 pmol/L plasma insulin. Both groups of obese women had mean fasting plasma insulin concentrations above this threshold level and, consequently, markedly suppressed IGFBP-1 levels. To assess the dynamics of insulin regulated IGFBP-1, 10 obese and 8 nonobese women were studied during sequential saline infusion (0-90 min), hyperinsulinemia (insulin infusion; 90-210 min) and hypoinsulinemia (somatostatin + GH infusion; 210-330 min). Insulin infusion rapidly decreased plasma IGFBP-1 levels in nonobese subjects (60% decrease in 2 h), but had little or no further suppressive effect in obese subjects. Complete insulin withdrawal resulted in a significant rise in plasma IGFBP-1 concentrations in all subjects, but the response was blunted in obese compared to nonobese groups. In contrast to plasma IGFBP-1, IGF-I concentrations did not vary during hyper- and hypoinsulinemic infusion periods and were not significantly different between groups. Basal GH levels were significantly higher in nonobese when compared to obese women, but did not change with infusions. In conclusion, low IGFBP-1 levels in obesity are related to elevated insulin levels which are, in turn, related to body fat distribution and insulin resistance. The chronically depressed levels of IGFBP-1 may promote IGF bioactivity as well as its feedback regulation of GH secretion, thus contributing to the metabolic and mitogenic consequences of obesity. In addition, our findings imply that hepatic insulin sensitivity in terms of IGFBP-1 production is preserved despite peripheral insulin resistance in obesity.
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PMID:Insulin regulation of insulin-like growth factor binding protein-1 in obese and nonobese humans. 137

The insulin-like growth factors (IGFs) are bound by specific, high affinity binding proteins. Distinct classes of IGF-binding proteins have been described in human serum, amniotic fluid, cerebrospinal fluid, and conditioned medium from cultured cells. Sheep thyroid cells produce IGF-binding proteins under hormonal regulation. Cells grown without or with standard medium supplements (transferrin, glycyl-histidyl-lysine, hydrocortisone, somatostatin, insulin, and TSH) released binding proteins with apparent mol wt of 23, 29, and 32 kDa on Western ligand blot (nonreduced). Binding proteins from these cells appeared as 21, 26, 34, 36, and 41 kDa bands when cross-linked to [125I]IGF-I under reducing conditions. The addition of epidermal growth factor (EGF) or phorbol esters, thyroid cell mitogens stimulated the production of larger binding proteins with mol wt of 40-44 and 48-52 by ligand blot and cross-linking methods, respectively. Deglycosylation of conditioned medium cross-linked to [125I]IGF-I with endoglycosidase-F did not alter the size of the smaller binding proteins, but reduced EGF-stimulated binding proteins to 36-40 kDa. Similarly, tunicamycin treatment, which inhibits glycosylation, reduced only the size of this larger binding protein species. Polyclonal antisera directed against the human amniotic fluid binding protein (BP-28) immunoprecipitated the 32 kDa sheep thyroid binding protein seen on ligand blot and the cross-linked binding protein at 36-38 kDa. Antibody against the major human serum binding protein (BP-53) recognized only the larger EGF-stimulated binding proteins. In contrast to sheep thyroid cells, rat FRTL5 thyroid cells produced no detectable IGF-binding proteins. We conclude that the predominant binding proteins produced by sheep thyroid cells under standard culture conditions are non-glycosylated and immunoreact with antiserum directed against BP-28. EGF and phorbol esters stimulate production of larger glycosylated binding proteins antigenically related to BP-53.
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PMID:Characterization of insulin-like growth factor-binding proteins from sheep thyroid cells. 247 27

The present study tested the hypothesis that a reduction in serum GH during adolescence would result in slower growth and delayed puberty. Skeletal growth and maturation as well as indices of reproductive development were studied in juvenile female rhesus monkeys receiving a constant sc infusion of a somatostatin analog, Sandostatin, at a dose of approximately 4.50 micrograms/kg BW.day (Ssa; n = 6) and in untreated females (Con; n = 6) from 18 months of age through the luteal phase of the second ovulation. Although age at menarche was similar in Con and Ssa females, first ovulation was delayed significantly in Ssa females, such that the interval between menarche and first ovulation was significantly longer in Ssa females. Serum concentrations of GH, insulin-like growth factor-I (IGF-I), and IGF-binding protein-3 were reduced in Ssa females, particularly after menarche. Although changes in body weight were similar between Ssa and Con females, growth in height was significantly greater in Con females. Furthermore, peak growth velocity in height occurred at a significantly later age in SSa females, but at a similar degree of skeletal maturity. Serum insulin and glucose levels in response to iv glucose were similar in the two groups; however, fasting levels of serum glucose decreased significantly in both groups with advancing age, but the decrease was greater in Con. During the luteal phase of the first 2 ovulatory cycles, there were diminished serum progesterone in 16.7% (2 of 12) of the Con and 41.7% (5 of 12) of the Ssa females. Serum estradiol was significantly lower throughout the first 2 ovulatory cycles in Ssa females, whereas serum LH and IGF-I were similar to those in Con females. Multiple regression analyses revealed that age at menarche was best predicted from the amount of growth in height before menarche, whereas those females who had higher serum IGF-binding protein-3 levels before menarche had an earlier growth spurt, and those who grew faster had a shorter interval between menarche and first ovulation. These data indicate that treatment with a long-acting somatostatin analog, which produces a relative deficiency in the GH axis, slows growth and delays the tempo of puberty. The data suggest that this delay may be due to a reduction in gonadal sensitivity to LH.
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PMID:Somatostatin analog treatment slows growth and the tempo of reproductive maturation in female rhesus monkeys. 751 92

In this study, we have found that IGF-binding protein-3 (IGFBP-3) in calf serum added to tissue culture medium is degraded by cultured FRTL-5 cells and a major 31 kDa fragment of IGFBP-3 is produced. When FRTL-5 rat thyroid cells were cultured in 6H medium (modified F-12M medium containing TSH, insulin, hydrocortisone, somatostatin, transferrin, and glycyl-histidyl-lysine) containing 5% calf serum, both 44-46 and 31 kDa IGFBPs were found in conditioned medium by ligand blot analysis using 125I-labelled IGF-II. However, predominantly the 44-46 kDa IGFBP was detected in unconditioned 6H medium containing 5% calf serum. When calf serum in the media was replaced by human serum similar results were obtained, and the 44-46 kDa and 31 kDa IGFBPs were recognized using a human IGFBP-3 antibody following Western blot analysis. FRTL-5 cells secreted only small amounts of an endogenous 29 kDa IGFBP, thought to be IGFBP-5. To separate the 31 kDa fragment of IGFBP-3 from the endogenous IGFBP-5, culture media were fractionated by concanavalin-A-Sepharose chromatography and aliquots of both flow-through and eluate from the column were analyzed by ligand blotting. A 31 kDa IGFBP was found in the eluate fractions from concanavalin-A-Sepharose chromatography following the separation of conditioned 6H medium supplemented with calf serum, suggesting that this species was an N-linked glycoprotein and could be derived from the degradation of serum IGFBP-3 by FRTL-5 cells. Using a modified zymographic assay, we examined whether the degradation of IGFBP-3 could depend on the cell membrane. Confluent FRTL-5 cells were washed with PBS and overlaid with liquid agarose solution. After the agarose had solidified, unconditioned 6H medium containing 5% calf serum was incubated with the cells at 37 degrees C for 16 h. Both 44-46 and 31 kDa IGFBP species were found in the overlying, conditioned medium by ligand blot. However, the 31 kDa IGFBP was not found in medium in the absence of FRTL-5 cells, and no IGFBP could be found in serum-free conditioned medium from agarose-covered FRTL-5 cells. This suggests that the 44-46 kDa IGFBP-3 in serum was degraded to yield a 31 kDa fragment, while any endogenous IGFBP-5 could not pass out of the agarose. The degradation of 44-46 kDa IGFBP-3 in the modified zymographic assay was inhibited by phenylmethylsulfonyl fluoride, EDTA, and aprotinin, but not by leupeptin. In summary, these results indicated that IGFBP-3 in calf serum added to culture medium could be degraded by FRTL-5 cells and that this may involve calcium-dependent serine proteases.
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PMID:Degradation of IGF-binding protein-3 by proteases in cultured FRTL-5 rat thyroid cells. 907 84

The effect of the somatostatin analogue octreotide on the secretion of progesterone and insulin-like growth factor binding protein-1 (IGFBP-1) from human granulosa-luteal cells was investigated. Octreotide (10(-11), 10(-10) and 10(-9) M) alone induced a significant decrease in progesterone secretion (maximum suppression 69 +/- 5% of control: P < 0.0001). In contrast, treatment with octreotide in combination with human chorionic gonadotrophin (HCG), at 1 IU/ ml potentiated the stimulatory effect of HCG on progesterone secretion (HCG alone 201 +/- 3% of control: HCG + octreotide 10(-9) M 318 +/- 16%: P < 0.001). Treatment with octreotide increased the secretion of IGFBP-1 (maximum stimulation 254 +/- 25% of control: P < 0.01). No effect of HCG was seen on secretion of IGFBP-1. These findings raise the possibility that somatostatin may have a modulatory role in regulating steroidogenesis by the human corpus luteum. Further studies are required to establish the physiological significance of any such function.
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PMID:The somatostatin analogue, octreotide, modifies both steroidogenesis and IGFBP-1 secretion in human luteinizing granulosa cells. 951 48

In adult female monkeys, serum concentrations of insulin-like growth factor I (IGF-I) are decreased by estradiol replacement, whereas levels of IGF-binding protein-3 (IGFBP-3) are increased. Furthermore, chronic IGF-I supplementation elevates serum IGFBP-3 despite a suppression of GH. To better understand how estradiol and IGF-I affect the IGF-I axis, a series of three studies was conducted to examine how estradiol and GH interact to affect the IGF-I axis and how IGF-I regulates IGFBP-1 and -3 during GH inhibition or receptor antagonism in adult female rhesus monkeys. In Exp 1, adult ovariectomized females were studied during a 28-day baseline condition and a 28-day treatment condition in which females received a constant s.c. infusion of a somatostatin analogue (octreotide, Sandoz; SSa; 6 microg/kg x day) with a 14-day washout period separating the two conditions. Within each 28-day phase, females were studied for 14 days with no estradiol replacement and for 14 days with estradiol replacement (3 microg/kg x day, s.c.). Treatment with estradiol and SSa alone significantly lowered serum IGF-I compared with baseline. In contrast, estradiol and SSa given in combination resulted in a significant increase in serum IGF-I. Serum IGFBP-3 was significantly increased by estradiol and the combination of estradiol and SSa. The response of serum GH to the acute administration of the excitatory amino acid analogue, n-methyl-D,L-aspartic acid (5 microg/kg, i.v.) was not differentially affected by any of the treatments. In Exp 2, the effects of a GH receptor antagonist (Trovert, Sensus Corp.) was assessed in ovariectomized, young adult, treated females (GHa; 1.0 mg/kg, s.c., weekly) and compared with that in untreated cohorts (Con) during 3 weeks of no estradiol and 3 weeks of estradiol replacement (3 microg/kg x day, s.c.). Serum IGF-I and IGFBP-3 were significantly suppressed in GHa compared with Con females. In Con females, estradiol replacement significantly decreased serum IGF-I and increased serum IGFBP-3. In contrast, estradiol replacement significantly elevated both serum IGF-I and IGFBP-3 in GHa females. In Exp 3, the effects of acute IGF-I administration (110 microg/kg, s.c.) were assessed during baseline conditions and during treatment with either GHa (1.0 mg/kg, s.c., weekly) or SSa (16 microg/kg, s.c. infusion) in young adult females during no estradiol replacement and during estradiol replacement (3 microg/kg x day, s.c.). Acute IGF-I administration produced a similar net increase in serum IGF-I during baseline and GHa or SSa treatment. Although serum IGFBP-3 was significantly reduced by both GHa and SSa, acute treatment with IGF-I produced a significant elevation in IGFBP-3, peaking by 3 h after treatment before returning to baseline at 7 h. Estradiol replacement elevated serum IGFBP-1 under baseline conditions as well as during GHa and SSa treatments. However, changes in serum insulin in response to the feeding patterns during the acute treatment with IGF-I, predicted changes in serum IGFBP-1. As GH secretion was inhibited during SSa, acute IGF-I had little effect on serum GH. Although acute IGF-I significantly suppressed serum GH by 3 h after treatment during baseline, the hypersecretion of GH during GHa treatment was unaffected by acute IGF-I. In conclusion, the results of the present analysis indicate that the effects of estradiol in postadolescent females on serum IGF-I are dependent on GH status, whereas estradiol consistently elevates serum IGFBP-3. Furthermore, acute IGF-I increases serum IGFBP-3 in females even during GH inhibition or receptor antagonism. Although overall serum concentrations of IGFBP-1 are elevated by estradiol and may be differentially affected by IGF-I treatment, acute changes in IGFBP-1 are more a consequence of changes in serum insulin in response to food intake. Taken together, these data suggest that IGFBP-3 is regulated by factors in addition to GH and that IGF-I can affect its own bioavailabi
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PMID:Effects of estradiol and exogenous insulin-like growth factor I (IGF-I) on the IGF-I axis during growth hormone inhibition and antagonism. 981 85

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

Two fundamentally different methods are currently used for the determination of free insulin-like growth factor-I (IGF-I): ultrafiltration by centrifugation (UF) and direct immunoradiometric assay (IRMA). The aim was to evaluate a commercial IRMA (DSL, Webster, TX, USA) and to compare it with UF. In the IRMA it is recommended that samples be incubated for 2 h at 5;C. When comparing samples (n = 8) incubated for 1 and 2 h, levels increased by 27 +/- 5% (P< 0.0001). When incubating samples at 22;C instead of 5;C, levels increased by 192 +/- 32% (P< 0.0001). Addition of IGF-binding protein-1 (IGFBP-1) to normal sera (n = 6) dose-dependently decreased ultrafiltered free IGF-I only (P< 0.0007). Similarly, UF was more sensitive than IRMA to addition of IGFBP-2 (P< 0.05). In healthy subjects (n = 35) IRMA yielded 20% higher levels than UF (1.09 +/- 0.09 vs 0.91 +/- 0.12 microg/L; P< 0.0001). IRMA and UF yielded similar results in healthy subjects treated with IGF-I (n = 5) or growth hormone (n = 7) and in acromegalic patients (n = 6) before and after somatostatin analogue treatment. However, marked differences were observed in conditions with elevated IGFBP-1 and -2. In type-1 diabetics (n = 23) ultrafiltered free IGF-I was more reduced than IRMA free IGF-I (38 +/- 9 vs 76 +/- 7% of matched controls (n = 13); P< 0.0001). In patients with chronic renal failure (n = 25), IRMA free IGF-I was identical to control levels (n = 13), whereas ultrafiltered free IGF-I was decreased by 51 +/- 7% (P< 0.0001). Similarly, women with anorexia nervosa (n = 9) studied before and after weight gain showed significant changes in ultrafiltered free IGF-I only (P< 0.03). In conclusion, IRMA was not very robust with respect to variations in sample incubation and this may bias results. IRMA generally yielded higher levels than UF, in accordance with the knowledge that IRMA measures free plus readily dissociable IGF-I. IRMA was less affected than UF by added IGFBP-1 and -2, and reductions in free IGF-I were better revealed by UF than IRMA.
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PMID:Determination of free insulin-like growth factor-I in human serum: comparison of ultrafiltration and direct immunoradiometric assay. 1147 78

To determine the role of IGF-binding proteins in mediating the direct effects of recombinant human IGF-I on insulin requirements in type 1(insulin-dependent) diabetes mellitus, overnight changes in IGF-I, IGF-II, and IGF-binding protein-1, -2, and -3, collected under euglycemic conditions, were compared in nine subjects after double blind, randomized, sc administration of recombinant human IGF-I (40 microg/kg) or placebo at 1800 h. On both nights a somatostatin analog infusion (300 ng/kg x h) suppressed endogenous GH production, and three timed discrete GH pulses (total, 0.029 IU/kg x night) ensured identical GH levels. After recombinant human IGF-I administration, IGF-I levels and the IGF-I/IGF-binding protein-3 ratio increased [mean +/- SEM:IGF-I, 401 +/- 22 ng/ml; placebo, 256 +/- 20 ng/ml (P = 0.0002); IGF-I, 0.108 +/- 0.006; placebo, 0.074 +/- 0.004 (P = 0.0003), respectively], and insulin requirements decreased (IGF-I, 0.12 +/- 0.03; placebo, 0.23 +/- 0.03 U/kg x min; P = 0.008). The normal within-individual inverse relationships between insulin and IGF-binding protein-1 levels were observed (lag time 2 h: r = -0.34; P < 0.01). Yet despite reduced free insulin levels (8.5 +/- 1.5; placebo, 12.2 +/- 1.2 mU/liter; P = 0.03), IGF-binding protein-1 levels were reduced after recombinant human IGF-I administration (53.7 +/- 6.8; placebo, 82.2 +/- 11.8 ng/ml; P = 0.008). The largest reductions in free insulin levels after recombinant human IGF-I and thus putative improvement in insulin sensitivity occurred in subjects with the smallest increase in the plasma IGF-I/IGF-binding protein-3 ratio (r = 0.7; P = 0.03). Taken together, these data are consistent with the hypothesis that transcapillary movement of IGF-I (perhaps mediated by IGF-binding protein-1), out of the circulation facilitates altered insulin sensitivity. These data have important implications for risk-benefit assessment of recombinant human IGF-I therapy in type 1 diabetes mellitus.
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PMID:The role of IGF-binding proteins in mediating the effects of recombinant human IGF-I on insulin requirements in type 1 diabetes mellitus. 1150 96

It was recently discovered that the streptozotocin (STZ)-diabetic mouse model is characterised by GH hypersecretion in contrast to the STZ-diabetic rat, the former thus mimicking the changes in GH in human type 1 diabetes. Inhibition of circulating and renal IGF-I by long-acting somatostatin analogues reduces renal and glomerular growth and urinary albumin excretion in diabetic rats. The aim of the present study was to examine renal and glomerular growth in early experimental diabetes in mice along with changes in the GH/IGF-I axis following treatment with the somatostatin analogue octreotide. Balb/C(a) mice were randomised into non-diabetic controls, placebo-treated and octreotide-treated diabetic (50 microg/day) mice and examined 7 and 14 days after induction of diabetes. There was no effect of octreotide treatment on body weight, glycaemic control or food intake. However, octreotide treatment significantly inhibited renal and glomerular growth by the end of the study period when compared with placebo treatment. In addition, octreotide prevented an increase in kidney IGF-I by day 7. GH hypersecretion was observed in the diabetic groups but octreotide treatment reduced GH levels compared with placebo treatment by day 14. No significant differences in serum or kidney IGF-binding protein-3 levels were observed between placebo- and octreotide-treated diabetic mice. In conclusion, this new diabetic mouse model mimicking human type 1 diabetes is characterised by GH hypersecretion and the somatostatin analogue octreotide is able to prevent renal and glomerular growth, probably mediated through changes in circulating GH and local kidney IGF-I levels.
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PMID:Inhibitory effects of octreotide on renal and glomerular growth in early experimental diabetes in mice. 1187 12


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