UMLS:C0432222 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-like growth factor II (IGF-II) is a human plasma peptide whose sequence is homologous to both insulin-like growth factor I/somatomedin C (IGF-I/SM-C) and human proinsulin in the A and B regions. However, there is no obvious homology in the C (connecting peptide) region. The synthetic 8-amino acid C-peptide segment of IGF-II (Ser-Arg-Val-Ser-Arg-Arg-Ser-Arg) was covalently linked to thyroglobulin to render it more antigenic. Antiserum against the IGF-II C-peptide was generated which had a titer of 1:2000 determined with [125I]IGF-II C-peptide. Half-maximum displacement was by 350 pg/ml IGF-II C-peptide or 80 ng/ml IGF-II. There was no displacement by IGF-I/SM-C, insulin, or a wide variety of peptides. There was also a high degree of species specificity of this antisera. Isoelectric focusing studies of immunoreactive IGF-II showed an apparent pI of 6-6.5. The mean (+/- SEM) level of IGF-II after acid chromatography of 28 normal adult males was 687.0 +/- 31.9 ng/ml. The mean of 8 acromegalics was 600.5 +/- 57.4 ng/ml, indistinguishable from normal. The IGF-II levels of 21 hypopituitary children were significantly lower (231.5 +/- 32.3 ng/ml). Thus, GH action appears to be necessary for normal levels of IGF-II, but excess GH does not cause an elevation above normal of IGF-II, unlike what is seen with IGF-I/SM-C. These structurally related IGF peptides have different control mechanisms and ultimately may play different functional roles. The availability of specific RIAs for the measurement of IGF-II will help to clarify its role in human physiology and disease states.
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PMID:A radioimmunoassay for insulin-like growth factor II specific for the C-peptide region. 617 44

The peripheral actions of growth hormone (STH) are mediated by somatomedins or "insulin-like growth factors" (IGF I and II). In untreated acromegaly (n = 24) IGF I was always found increased, IGF II, however, was unchanged. The mean IGF-I-level (+/- SEM) was 553 +/- 75 (range 319-1066) ng/ml in active acromegaly and 193 +/- 10 (range 120-300) ng/ml in control persons. The corresponding IGF-II-values were 533 +/- 38 (range 187-720) and 647 +/- 21 (range 400-900) ng/ml. After treatment of acromegaly IGF I followed changes of the basal STH level with a delay of 4-8 weeks independent of the mode of treatment. This was in contrast to behaviour of IGF II. When STH was suppressible below 1 ng/ml after oral administration of 100 g glucose IGF I was never increased. STH after glucose of more than 5 ng/ml was always associated with increased IGF I. STH values between 1 and 5 ng/ml after glucose were combined with IGF-I-increases in 3 out of 6 cases. Thus, IGF I represents a valuable diagnostic criterion for assessment of activity of acromegaly, particularly in borderline cases, in contrast to IGF II. The criterion of normal somatotrophic function is suggested to be suppressibility of STH level below 1 ng/ml after oral administration of 100 g glucose.
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PMID:[Diagnosis in acromegaly. Insulin-like growth factor as a parameter of activity]. 634 61

The somatomedin C/insulin-like growth factor I (SMC/IGF-I) response to human GH (hGH) therapy and the t1/2 of SMC/IGF-I after the cessation of hGH were determined in 15 children with GH deficiency. After 5 injections of hGH (0.1 U/kg), there was a significant increase in total SMC/IGF-I [from 0.27 +/- 0.06 to 1.19 +/- 0.17 U/ml (mean +/- SEM)]. Both the pretreatment SMC/IGF-I and the maximal SMC/IGF-I levels attained were correlated with chronological age and bone age. Body size, as indicated by height and weight, also correlated with pretreatment and maximal SMC/IGF-I levels. For both pretreatment and maximal SMC/IGF-I levels, there was a better correlation of SMC/IGF-I levels with bone age than with chronological age. While the correlation between height and the pretreatment SMC/IGF-I level was stronger, weight was a better predicter of the maximal SMC/IGF-I level. Maximal SMC/IGF-I levels were reached 18.8 +/- 2.9 h after the last hGH injection. The t1/2 for SMC-IGF-I after the attainment of maximal levels was 20.7 +/- 2.3 h, or 39.5 +/- 3.8 h from the last injection of hGH. The t1/2 of SMC/IGF-I determined in this way was longer than previous values reported from studies in the rat. The relatively long t1/2 of SMC/IGF-I which we observed may in part explain the success of present GH treatment regimens which involve every other day injections of hGH.
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PMID:Kinetics of the somatomedin C/insulin-like growth factor I: response to exogenous growth hormone (GH) in GH-deficient children. 703 25

To test the hypothesis that a dysfunctional growth hormone (GH)-insulin-like growth factor (IGF) axis may play a role in the pathogenesis of osteoporosis, we compared the levels of IGF-I, IGF-II and IGF binding protein 3 (IGFBP-3) in 15 women with spinal osteoporosis (i.e. at least one non-traumatic vertebral fracture) and 15 normal age-matched women. Furthermore, the response to 3 days' treatment with recombinant human GH (r-hGH) (0.2 IU kg-1.day-1) was determined. The basal levels of IGF-I, IGF-II and IGFBP-3 were similar in patients and controls (mean +/- SEM): IGF-I, 16.5 +/- 1.3 versus 16.0 +/- 1.3 nmol/l (NS); IGF-II, 79.9 +/- 3.6 versus 72.5 +/- 4.1 nmol/l (NS); and IGFBP-3, 125.7 +/- 6.5 versus 130.3 +/- 7.8 nmol/l (NS). Stimulation with r-hGH elicited increased levels of IGF-I, IGF-II and IGFBP-3 within both groups (p < 0.001). The maximal values expressed as a percentage of baseline were: IGF-I, 341 +/- 26% versus 369 +/- 22%, IGF-II, 125 +/- 4% versus 119 +/- 5%, IGFBP-3, 141 +/- 5% versus 147 +/- 7% in osteoporotic patients and controls, respectively. No significant differences were observed between patients and controls in either their maximal response or in the area under the response curves. Our results do not support the hypothesis of a dysfunctional GH-IGF axis in women with spinal osteoporosis.
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PMID:No evidence for reduced spontaneous or growth-hormone-stimulated serum levels of insulin-like growth factor (IGF)-I, IGF-II or IGF binding protein 3 in women with spinal osteoporosis. 752 Dec 46

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

To evaluate the possibility that insulin-like growth factors (IGFs) and their binding proteins (BPs) in bone play a role in regulating cortical bone formation in growing animals, we compared changes in IGF and IGF BP levels with changes in bone mineral density (BMD) at three different regions (proximal, middle, and distal) along the rabbit femoral shaft. BMD measured by dual-energy x-ray absorptiometry decreased progressively from proximal to distal regions of the shaft, from 0.449 +/- 0.005 to 0.354 +/- 0.002 g/cm2 (mean +/- SEM; n = 9), respectively; total protein concentrations also decreased toward the distal region. We extracted the IGFs and their BPs from bone by demineralization in 10% EDTA and 4 M guanidine-HCl (pH 4.5). The IGFs were then separated from their BPs by size exclusion HPLC. The pH of the extraction buffer profoundly influenced the recoveries of the IGFs and, to a lesser extent, the total protein; at least 100% more IGFs were recovered at acid (4.5) pH than at neutral (7.5) or basic (10.5) pH. The levels of IGF-I decreased markedly from proximal to distal regions, from 273 +/- 27 to 100 +/- 38 ng human IGF-I equivalent/g bone (or 103 +/- 10 to 52 +/- 11 ng human IGF-I equivalent/mg protein), respectively. IGF-II was uniformly distributed (385 +/- 17 ng human IGF-II equivalent/g bone; mean of all three regions). Levels of the predominant 28-32 kD IGF BP doublet increased by about 100% from proximal to distal segments, regardless of whether the data were expressed per unit mass or protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential distribution of insulin-like growth factors and their binding proteins within bone: relationship to bone mineral density. 753 48

The liver is thought to be the major source of circulating insulin-like growth factor (IGF-I) and IGF-binding protein-1 (IGFBP-1), whereas the primary production site of circulating IGFBP-3 remains unknown. As other tissues may contribute to the circulating pool of IGF-I and IGFBP, the aim of the present study was to assess the hepatic and renal arterio-venous difference and production rates of IGF-I, IGFBP-1, IGFBP-3, and GH in cirrhotic patients (n = 22) and matched control subjects (n = 27). IGFBP-1 and -3, IGF-I, and GH levels were measured by RIA in hepatic, renal, and peripheral veins and in the femoral artery. Levels of IGFBP-1 to -4 were additionally determined by Western ligand blotting. Hepatic venous IGFBP-1 was significantly increased in the cirrhotic patients (mean +/- SEM, 33.6 +/- 9.1 vs. 10.4 +/- 1.9 micrograms/L; P < 0.001), and arterio-renal-venous extraction was significant in both patients (6 +/- 2%; P < 0.01) and controls (11 +/- 1%; P < 0.001). Conversely, IGFBP-3 was decreased in the cirrhotic patients (1265 +/- 149 vs. 2712 +/- 137 micrograms/L; P < 0.001). IGFBP-3 correlated significantly with the wedged hepatic venous pressure (r = -0.49; P < 0.05), serum aspartate aminotransferase (r = -0.66; P < 0.01), serum bilirubin (r = -0.65; P < 0.01), serum albumin (r = 0.64; P < 0.01), and the Child score (r = -0.57; P < 0.01). IGF-I was significantly lower in the cirrhotics (57 +/- 10 vs. 143 +/- 11 micrograms/L; P < 0.001). No significant IGFBP-3 proteolysis was demonstrated in cirrhotics or controls. No significant differences were found in the values obtained simultaneously from hepatic, renal, and brachial veins or femoral artery, which suggests that no major net production or release of IGFBP-3 or IGF-I occurs in these tissues. No differences in IGFBP-2 or IGFBP-4 determined by Western ligan blot were found between patients and controls. The IGF-I concentrations correlated significantly with parameters of biochemical liver function. Basal GH concentrations were significantly higher in the cirrhotics (1.19 +/- 0.13 vs. 0.58 +/- 0.08 micrograms/L; P < 0.001). A significant hepatic disposal of GH was found in the patients (P < 0.05) and controls (P < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Concentrations, release, and disposal of insulin-like growth factor (IGF)-binding proteins (IGFBP), IGF-I, and growth hormone in different vascular beds in patients with cirrhosis. 753

The purpose of this study was to determine the effects of recombinant human GH (rhGH; 0.025 mg/kg.day) and one of two doses of recombinant human insulin-like growth factor-I (rhIGF-I; 0.015 and 0.060 mg/kg, twice daily) on body composition in elderly women. Sixteen healthy elderly women (mean age +/- SEM, 71.9 +/- 1.3 yr) were randomly assigned to receive either rhGH (GH; n = 5), low dose rhIGF-I (n = 6), or high dose rhIGF-I (n = 5). A 2-week predrug baseline period was followed by 4 weeks of hormone treatment, with a standardized diet fed throughout. All groups experienced a significant increase in serum IGF-I and IGFBP-3 levels over the treatment period, accompanied by significant decreases in IGF-II (P < 0.05). Fat mass decreased in all groups, with significant increases in lean body mass and nitrogen retention occurring in the high dose IGF and GH groups. Total body water did not change, whereas increases observed in intracellular fluid approached significance (P = 0.06). These anabolic changes were accompanied by numerous negative side-effects in the GH and high dose IGF groups, including headaches, lethargy, joint swelling/pain, and bloatedness. The low IGF dose was well tolerated. These results demonstrate that the administration of rhGH and rhIGF-I for 4 weeks results in anabolic changes in body composition in elderly women.
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PMID:The effects of recombinant human insulin-like growth factor-I and growth hormone on body composition in elderly women. 753 17

Obesity is associated with suppressed growth hormone (GH) concentrations but relatively little is known about insulin-like growth factors(IGFs) and binding proteins for GH and IGFs (GHBP and IGFBPs) and the modulatory effect of GH administration. In a double-blind, crossover design we studied the impact of 5 weeks of placebo or GH administration (0.03 mg.kg-1 body wt.day-1) in nine obese women (mean +/- SEM: age 30.4 +/- 2.4 years; body mass index 37.0 +/- 2.8 kg/m2) on IGF-I, IGF-II, IGFBP-1 and -3 and GHBP. Serum IGF-I (microgram/l) levels were subnormal and increased significantly following GH (117 +/- 16 (placebo) vs 434 +/- 33 (GH) vs 198 +/- 15 (control (p < 0.01)). By contrast, serum IGF-II (microgram/l) levels were in the normal range and remained unchanged (608 +/- 20 (placebo) vs 647 +/- 40 (GH) (NS)). Serum IGFBP-3 was in the normal range and increased significantly during GH treatment, although relatively less than IGF-I, such that the molar ratio between IGF-I and IGFBP-3 increased with GH treatment, whereas the ratio between IGF-I + IGF-II and IGFBP-3 remained unchanged. Serum IGFBP-1 was low in the placebo situation but became further and almost completely suppressed during GH treatment. During a 2-h hyperinsulinemic, euglycemic glucose clamp, IGFBP-1 decreased in the placebo study and remained suppressed during GH. Serum GHBP (nmol/l) levels were elevated substantially compared to non-obese controls (p < 0.001) and did not change during GH treatment (2.37 +/- 0.36 (placebo) vs 2.21 +/- 0.25 (GH) vs 0.80 +/- 0.19 (control)).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum concentrations of insulin-like growth factors (IGFs), IGF binding proteins 1 and 3 and growth hormone binding protein in obese women and the effects of growth hormone administration: a double-blind, placebo-controlled study. 754 82

Ovulation rate, serum hormone concentrations, follicular fluid (FFL) concentrations of steroids and IGF, IGF binding protein (IGFBP) activity in FFL, and follicular IGF-I and -II mRNA were compared during the follicular phase among five genotypes of ewes: Finn (F), Composite III (C), 1/2 Booroola Merino (B) x 1/2 F (B x F), 1/2 F x 1/2 C (F x C), 1/2 B x 1/2 C (B x C). Composite III ewes were a Columbia x Suffolk x Hampshire crossbred. Ovulation rates for F (n = 7), C (n = 5), B x F (n = 6), F x C (n = 3), and B x C (n = 8) ewes were 3.1, 1.6, 3.8, 2.9, and 2.9 (Pooled SEM = .5), respectively. Concentrations of IGF-I in FFL were 53% greater (P < .05) in large (> or = 4.1 mm) than in small (< 4.1 mm) follicles but did not differ (P > .10) among genotypes. In contrast, FFL IGF-II concentrations were greater (P < .05) in B x C and B x F ewes than in C or F x C ewes but did not differ between small and large follicles. Ligand blotting revealed that IGFBP activity of three species (34, 27 to 29, and 24 kDa) were lower (P < .05) in FFL of large than in FFL of small follicles but did not differ (P < .10) among genotypes. Follicular wall IGF-I mRNA and IGF-II mRNA was detected in 5 and 32% of the samples from preovulatory follicles, respectively, using reverse transcriptase-PCR and ethidiumbromide staining. Ovarian IGF-I mRNA levels, assessed by Northern analysis, in B x F and B x C ewes were greater (P < .05) than those in C ewes; ovarian IGF-I mRNA levels in F and F x C ewes were intermediate and did not differ (P > .10) from those in C ewes. Small follicles from B x C and B x F ewes had severalfold greater (P < .05) estradiol concentrations than those from F or C ewes, whereas large follicles from B x F ewes had twice (P < .05) the estradiol concentrations of follicles from F or C ewes. Progesterone in FFL did not differ among genotypes. Serum LH, FSH, inhibin, IGF-I, and progesterone did not differ (P > .10) among genotypes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Serum hormones, follicular fluid steroids, insulin-like growth factors and their binding proteins, and ovarian IGF mRNA in sheep with different ovulation rates. 754 85

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