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Biomedical subjects

A Flyvbjerg

Publications and source records attributed to A Flyvbjerg.

At least 109 records · Page 6Linked to original sources
PubMed1999

Low serum levels of free and total insulin-like growth factor I (IGF-I) in patients with anorexia nervosa are not associated with increased IGF-binding protein-3 proteolysis.

Patients with anorexia nervosa (AN) are GH resistant, with elevated GH levels and low serum levels of total insulin-like growth factor I (IGF-I). IGF-I action is modulated by IGF-binding proteins (IGFBPs), and a variety of catabolic states has been characterized by the presence of increased IGFBP-3 proteolysis. The present study was performed to examine the levels of free IGFs in AN and to clarify whether AN is associated with increased IGFBP-3 proteolytic activity. In 24 patients and 10 age-matched controls, the fasting serum concentrations of free IGF-I and -II were measured using ultrafiltration by centrifugation. In addition, GH, GH-binding protein, total IGFs, IGFBP-1 to -4, and IGFBP-3 proteolytic activity were measured. The IGFBPs were measured by both immunoassays and Western ligand blotting. Twelve of the patients were restudied 3 months after a minor increase in body mass index. In AN, the levels of GH-binding protein, free and total IGF-I, free IGF-II, and IGFBP-3 were significantly reduced; total IGF-II, IGFBP-2, and IGFBP-4 levels were unchanged; and IGFBP-1 was increased. No increased IGFBP-3 proteolytic activity could be detected in AN. In conclusion, the mechanisms responsible for the adaption of the GH-IGF-IGFBP axis in AN may be different from other catabolic conditions, because the low levels of free and total IGF-I in AN are not associated with increased IGFBP-3 proteolysis.

Adult↗
PubMed1999

Jointly amplified basal and pulsatile growth hormone (GH) secretion and increased process irregularity in women with anorexia nervosa: indirect evidence for disruption of feedback regulation within the GH-insulin-like growth factor I axis.

Anorexia nervosa (AN) is associated with multiple endocrine alterations. In the majority of AN patients, basal and GHRH-stimulated serum GH levels are increased. The metabolic effects of GH are known to be related to its pulsatile secretory pattern. The present study was performed to examine GH pulsatility in AN using the techniques of deconvolution analysis and approximate entropy, which quantify secretory activity and serial irregularity of underlying hormone release not reflected in peak occurrence or amplitudes. To this end, 24-h GH profiles were obtained by continuous blood sampling aliquoted at 20-min intervals in 8 nonfasting patients with AN [body mass index (BMI), 14.2 +/- 0.8 kg/m2; mean +/- SEM) and in 11 age-matched healthy women (BMI, 20.3 +/- 0.5 kg/m2). The deconvolution-estimated half-life of GH was not altered in the AN patients. The pituitary GH secretory burst frequency, burst mass, and burst duration were each significantly increased in women with AN compared to those in normal weight women. A 4-fold increase in daily pulsatile GH secretion was accompanied by a 20-fold increase in basal (nonpulsatile) GH secretion. There were significant negative correlations between BMI and the basal as well as pulsatile GH secretion rates. Moreover, AN patients exhibited significantly greater GH approximate entropy scores than the controls, denoting marked irregularity of the GH release process. In contrast to previous reports in healthy fasting subjects, cortisol levels in AN patients were positively correlated to GH secretion rates. Leptin levels were significantly inversely correlated to the pulsatile, but not the basal, GH secretion rate. The present data demonstrate augmented basal as well as pulsatile GH secretion with disruption of the orderliness of the GH release process in AN. Accordingly, GH secretion in AN probably reflects altered neuroendocrine feedback regulation, e.g. associated with increased hypothalamic GHRH discharge superimposed on reduced hypothalamic somatostatinergic tone.

Activity Cycles↗
PubMed1999

Growth hormone receptor antagonism prevents early renal changes in nonobese diabetic mice.

The growth hormone (GH)/insulin-like growth factor (IGF) axis is involved in diabetic renal disease. The role of a specific GH receptor (GHR) antagonist in the development of early renal changes in nonobese diabetic (NOD) mice was investigated. Female diabetic (nonketotic) NOD mice treated with a polyethylene glycol-treated GHR antagonist (2 mg/kg, every other day) (DA group) or saline (D group) and their nonhyperglycemic age-matched littermates (control animals) were euthanized 3 wk after the onset of diabetes. Body weights at euthanasia were similar among the groups. Serum GH levels were markedly elevated, and serum IGF-I levels were significantly decreased in D and DA animals, compared with controls. The increases in kidney weights and glomerular volumes observed for the D group were absent in the DA group. Albuminuria was increased in the D group but was normalized in the DA group. Extractable renal IGF-I protein levels were increased in the D group but were partially normalized in the DA group. Renal IGF-binding protein 1 mRNA levels were increased in the D group but returned to almost normal levels in the DA animals. Kidney IGF-I and GHR mRNA levels were decreased in both the D and DA groups. Renal GH-binding protein mRNA levels remained unchanged in both diabetic groups. GHR antagonism had a blunting effect on renal/glomerular hypertrophy and albuminuria in diabetic NOD mice. These salutary effects were associated with concomitant inhibition of increased renal IGF-I protein levels and were obtained without affecting either somatic growth or circulating GH and IGF-I levels. Therefore, modulation of GH effects may have beneficial therapeutic implications in diabetic nephropathy.

Animals↗
PubMed1999

Phosphorylated insulin-like growth factor binding protein 1 is increased in pregnant diabetic subjects.

During pregnancy, IGFs and their binding proteins (IGFBPs) are important for the growth of fetal and maternal tissues. IGFBP-1 normally circulates as a single, highly phosphorylated species (hpIGFBP-1). However, in pregnancy there are lesser phosphorylated isoforms (lpIGFBP-1) with decreased affinity for IGF-I, allowing for increased IGF bioavailability. Because regulation of IGFBP-1 is abnormal in type 1 diabetes, we examined the impact of this on IGFBP-1 and its phosphorylation status in diabetic pregnancy. We assessed IGFBP-1 in relation to birth weight, maternal weight gain, duration of diabetes, glycemic control, and the presence or absence of retinopathy in 44 diabetic and 11 nondiabetic subjects. We found that in type 1 diabetic patients there was a significant negative relationship between hpIGFBP-1 and birth weight (r = -0.42, P < 0.01) and between the ratio of hpIGFBP-1 to lpIGFBP-1 and birth weight (r = -0.38, P = 0.02) by week 18 of gestation. Multiple regression analysis confirmed that hpIGFBP-1 was the best single predictor of birth weight (R2 = 0.3, P = 0.001) in diabetic subjects using models including other parameters known to influence fetal size. In contrast to hpIGFBP-1 levels, lpIGFBP-1 levels were not associated with birth weight, but were significantly related to initial maternal BMI and maternal weight throughout gestation in diabetic subjects (r = -0.57, P < 0.001). hpIGFBP-1 levels were positively related to duration of diabetes (r = 0.38, P < 0.01). Diabetic subjects had significantly higher hpIGFBP-1 and lpIGFBP-1 levels than nondiabetic subjects (hpIGFBP-1: 215 +/- 21 vs. 108 +/- 13 microg/l, P = 0.01; lpIGFBP-1: 139 +/- 12 vs. 66 +/- 5 microg/l, P < 0.001), but the ratio of hpIGFBP-1 to lpIGFBP-1 was similar in both groups (2.1 +/- 0.3 [diabetic] vs. 1.7 +/- 0.2 [nondiabetic], NS). In summary, maternal IGFBP-1 levels were higher in diabetic than in normal pregnancies. Diabetic subjects with prolonged duration of diabetes and retinopathy had higher total IGFBP-1 levels than those with shorter disease duration. Thus hpIGFBP-1 in diabetic pregnancy is positively related to the duration of diabetes and inversely related to fetal growth, with lpIGFBP-1 being related to maternal weight and BMI. The ratio of hpIGFBP-1 to lpIGFBP-1 may be a more robust indicator of fetal outcome, since it was consistent between diabetic and nondiabetic subjects. Measurement of the different phosphorylated isoforms of IGFBP-1 may increase the usefulness of IGFBP-1 as a predictor of fetal growth in both normal and diabetic pregnancy.

Adult↗
PubMed1999

Inhibitory effect of a growth hormone receptor antagonist (G120K-PEG) on renal enlargement, glomerular hypertrophy, and urinary albumin excretion in experimental diabetes in mice.

Growth hormone (GH) and IGFs have a long and distinguished history in diabetes, with possible participation in the development of renal complications. To investigate the effect of a newly developed GH receptor (GHR) antagonist (G120K-PEG) on renal/glomerular hypertrophy and urinary albumin excretion (UAE), streptozotocin-induced diabetic and nondiabetic mice were injected with G120K-PEG every 2nd day for 28 days. Placebo-treated diabetic and nondiabetic animals were used as reference groups. Placebo-treated diabetic animals were characterized by growth retardation, hyperphagia, hyperglycemia, increased serum GH levels, reduced serum IGF-I, IGF-binding protein (IGFBP)-3, and liver IGF-I levels, increased kidney IGF-I, renal/glomerular hypertrophy, and increased UAE when compared with nondiabetic animals. No differences were seen between the two diabetic groups with respect to body weight, food intake, blood glucose, serum GH, IGF-I, and IGFBP-3 levels or hepatic IGF-I levels. Kidney IGF-I, kidney weight, and glomerular volume were normalized, while the rise in UAE was partially attenuated in the G120K-PEG-treated diabetic animals. No effect of G120K-PEG treatment on any of the parameters mentioned above was seen in nondiabetic animals. In conclusion, administration of a GHR antagonist in diabetic mice has renal effects without affecting metabolic control and circulating levels of GH, IGF-I, or IGFBP-3, thus indicating that the effect of G120K-PEG may be mediated through a direct inhibitory effect on renal IGF-I through the renal GHR. The present study suggests that specific GHR blockade may present a new concept in the treatment of diabetic kidney disease.

Albuminuria↗
PubMed1998

Effect of immunosuppression on kidney and serum insulin-like growth factor-I (IGF-I), IGF binding proteins, and renal growth following unilateral nephrectomy in rats.

A rat model was used to study the role of renal insulin-like growth factor-I (IGF-I) and circulating IGF-I and IGF binding proteins (IGFBPs) in early posttransplantation renal hypertrophy and overall body growth during high-dose immunosuppression. Seven days of prednisolone and cyclosporin A (CsA) immunosuppression was administered to rats following unilateral nephrectomy compared with sham-operated controls. Immunosuppression of nephrectomized and control rats was followed by a reduction in body weight (BW) compared with placebo treatment. In addition, immunosuppression inhibited kidney IGF-I accumulation and compensatory renal growth in uninephrectomized rats, but caused no change in kidney weight or IGF-I levels in control rats. Immunosuppression induced a sustained significant increase in circulating IGFBP-3 and 30-kd IGFBPs in uninephrectomized and controls rats, whereas serum IGF-I levels were unchanged. In a supplementary study separating the effects of the two immunosuppressants, the kidney IGF-I changes and renal growth were primarily affected by CsA, while the changes in IGFBPs appeared to be caused by prednisolone treatment. In conclusion, immunosuppression with prednisolone and CsA was followed by less kidney IGF-I accumulation and compensatory renal growth compared with placebo treatment. In addition, a sustained increase in circulating levels of IGFBP-3 and 30-kd IGFBPs was observed, which may be involved in the growth impairment observed following immunosuppressive treatment.

Animals↗
PubMed1998

Gene expression of insulin-like growth factor-I, its receptor and binding proteins in retina under hypoxic conditions.

Hypoxia is the main stimulus for neovascularization in the retina. Insulin-like growth factor-I (IGF-I) is thought to be one of the mediators of this process. Severe persistent hypoxia, as occurs in central retinal artery occlusion, is associated with less retinal neovascularization than relative hypoxia. To study the influence of different types of hypoxia on the IGF system, we used a model of neonatal rat retina that responds with neovascularization to a relative hypoxic stimulus produced by alternating oxygen concentrations in the respired air. We studied the influence of 24-hour hypoxia (10% oxygen), 48-hour hyperoxia (75% oxygen), and relative hypoxia (shifting from 48 hours in 75% oxygen to 24 hours in room air) on the gene expression of IGF-I, IGF-I receptor (IGF-IR), and IGF binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 in retina using a solution hybridization RNase protection assay. Hypoxia induced a significant increase in retinal IGF-IR (178%), IGFBP-2 (227%), and IGFBP-3 (317%) mRNA; however, retinal IGF-I mRNA was reduced, as well as serum growth hormone (GH). Relative hypoxia caused a similar but less pronounced trend in the gene expression of IGF-IR and the binding proteins, whereas retinal IGF-I mRNA was unchanged and serum GH was elevated. Both hypoxia and relative hypoxia may cause IGF system stimulation in the retina through upregulation of IGF-IR and IGFBPs. This stimulation may result in neovascularization. However, during hypoxia, low levels of tissue oxygenation and reduced local production of IGF-I may impede the neovascularization process.

Animals↗
PubMed1998

Systemic treatment with epidermal growth factor causes organ growth concomitant with reduced circulating levels of IGF-I and IGFBP-3: time-dependent changes in female rats.

Systemic treatment with epidermal growth factor (EGF) in neonatal rats reduces circulating levels of insulin-like growth factor I (IGF-I) and causes somatic growth retardation. In this study, we investigated the effects of EGF treatment on the IGF system and on visceral organ growth and longitudinal growth in mature rats. We treated female Wistar rats for 0 (n = 16), 1 (n = 8), 2 (n = 8), 3 (n = 8), or 4 (n = 8) weeks with subcutaneous EGF (150 microg/kg/day). The animals were weighed once a week. At sacrifice, various viscera were removed and weighed. Blood and serum samples obtained at sacrifice were analysed for growth hormone (GH), IGF-I, IGF binding proteins (IGFBPs) and various routine parameters. EGF treatment increased the total body weight. All parts of the gastrointestinal tract, the liver, the pancreas, the spleen, the bladder, the suprarenal glands and the ovaries increased proportionately more in weight than the increase in total body weight; the heart and the kidneys increased proportionately in weight whereas the weight of the perirenal fat was reduced. There were no changes in tail length but the mean length of the tibia was slightly increased in the group treated for 4 weeks with EGF. Circulating GH was unchanged but IGF-I and IGFBP-3 were reduced approximately 25 and 45%, respectively, in all EGF treated groups. There were no changes in the hepatic content of IGF-I and IGFBPs. In conclusion, systemic EGF treatment causes visceral growth concomitant with reduced circulating levels of IGF-I and IGFBP-3 in mature female rats.

Animals↗
PubMed1998

Differential expression of renal growth hormone receptor and its binding protein in experimental diabetes mellitus.

Growth hormone (GH) may have a role in the development of diabetic nephropathy. The effect of experimental diabetes on renal expression of the growth hormone receptor gene products, including the receptor itself (GHR) and its binding protein (GHBP) was examined. Adult female rats received i.v. streptozotocin and were killed at 7, 30, 90 and 180 days after the induction of diabetes. Diabetic animals had a pronounced increase in kidney weight and progressive albuminuria. In renal cortex, no change was seen in GHR mRNA levels throughout the observation period of 6 months, while a significant increase in cortical GHBP mRNA levels was observed after 1 month of diabetes and sustained for the rest of the study period. Immunohistochemical analysis of kidney sections revealed a stronger staining for GHBP at the cortical and inner medullary areas in the diabetic animals. These data indicate that although the GHR and GHBP mRNAs originate from the same gene, their renal levels are differentially regulated during the development of experimental diabetic kidney disease, suggesting a functional role for GHBP.

Albuminuria↗
PubMed1998

The organ extraction and splanchnic haemodynamic effects of octreotide in cirrhotic patients.

BACKGROUND: Intravenous octreotide is an established treatment of oesophageal variceal haemorrhage in the cirrhotic patient. AIM: To examine the organ extraction and splanchnic haemodynamic effects of octreotide in cirrhotic patients with portal hypertension. METHODS: Thirteen patients with cirrhosis had hepatic venous catheterization performed. Hepatic venous pressure gradient (HVPG), indocyanine green (ICG) clearance and hepatic blood flow (HBF) were determined in the basal state and during 60 min of octreotide infusion by bolus injection (0.75 microg/kg) followed by continuous infusion of 0.75 microg/kg x h. Blood samples were simultaneously drawn from the femoral artery and the hepatic and renal veins. RESULTS: The extraction fraction of octreotide in the liver was 0.05 (-0.01 - 0.14) (median (interquartile range)) and in the kidneys 0.16 (-0.06 - 0.35). The extraction fraction ratio (E(liver)/E(kidney)) was 0.69 (-0.20 - 1.06). Hepatic clearance was 47 mL/min (3-88) (n = 11). No correlations were found between liver biochemistry or galactose elimination capacity (GEC; a metabolic measure of liver function) and renal extraction fraction or liver clearance. Octreotide had no effect on HVPG or wedged hepatic venous pressure although free hepatic venous pressure increased during octreotide infusion: 6 mmHg (5-9) vs. 7 mmHg (6-10) (P = 0.02). No effect on HBF was observed while ICG clearance decreased significantly. CONCLUSIONS: Octreotide is extracted in cirrhotic patients by both the liver and the kidney, the latter being the most important organ of elimination. Octreotide decreases liver metabolic activity determined by the ICG clearance technique, but no significant effects of octreotide on HVPG or HBF could be demonstrated.

Adult↗
PubMed1998

Effects of growth hormone treatment on serum levels of insulin-like growth factors (IGFs) and IGF binding proteins 1-4 in postmenopausal women.

BACKGROUND AND OBJECTIVE: Insulin-like growth factor binding proteins (IGFBPs) modulate the actions and bioavailability of insulin-like growth factors (IGFs), however, their regulation in vivo is incompletely understood. In this study we investigated the effects of different doses of growth hormone (GH) on circulating levels of IGFs and IGFBPs. DESIGN: The study was double-blind and placebo-controlled. Patients were treated with either GH in doses of 0.05, 0.10, or 0.20 lU/kg/day of placebo for one week. PATIENTS: Forty post-menopausal women aged 52-73 years with low bone mass. MEASUREMENTS: Serum IGF-I and IGF-II were measured by RIA while IGFBP-1-3 were measured by Western ligand blot (WLB) and compared with determinations by specific immunoassays. IGFBP-4 was measured by WLB alone. RESULTS: Both IGF-I (P < 0.001) and IGF-II (P < 0.01) increased significantly during GH treatment. Additionally, IGFBP-1 (P < 0.001) and IGFBP-2 (P < 0.001) decreased significantly while IGFBP-3 (P < 0.001) and IGFBP-4 (P < 0.05) increased all in a dose-dependent manner. Stepwise (backwards) multiple regression analyses showed that the changes in IGF-I and IGF-II, and age correlated with the change in serum IGFBP-1. Both GH-dosage, the increase in IGF-II, and body mass index correlated with the decrease in IGFBP-2. Furthermore, the increase in serum IGF-I, IGF-II, and triiodothyronine correlated with the increase in IGFBP-3. Moreover, GH-dosage correlated with the increase in serum IGFBP-4. CONCLUSION: GH significantly increased serum IGF-I, IGF-II, IGFBP-3, and IGFBP-4 and decreased serum IGFBP-1 and IGFBP-2 in post-menopausal women.

Aged↗
PubMed1998

Effect of octreotide, captopril or insulin on renal changes and UAE in long-term experimental diabetes.

Renal and glomerular growth is inherent in early human and experimental diabetes frequently followed by later increase in urinary albumin excretion (UAE). Treatment with angiotensin converting enzyme (ACE) inhibitors has proven effective in delaying progression of human and experimental diabetic renal changes, and so has somatostatin analog treatment in experimental diabetes. The aim of the present study was to investigate three weeks of octreotide and captopril treatment alone or in combination following three months of untreated experimental diabetes, and compare the effects to those of insulin treatment. Diabetes induced significant increases in renal and glomerular growth and urinary albumin excretion. Octreotide and captopril alone and in combination reduced renal but not glomerular size, and the combined administration reduced UAE. None of these schedules affected blood glucose levels. Insulin treatment inducing euglycemia significantly reduced renal and glomerular size and UAE. In conclusion, insulin treatment with normalization of the diabetic metabolic derangement nearly normalizes renal and glomerular growth and UAE after three months of untreated diabetes. The combined treatment of octreotide and captopril was also followed by a significant decrease in renal growth and reduction in UAE compared to placebo treatment without affecting the metabolic control of the diabetic animals.

Albuminuria↗
PubMed1998

The endogenous insulin-like growth factor system in radiocontrast nephropathy.

The response of insulin-like growth factor (IGF) I in acute renal failure was evaluated in a model of radiocontrast nephropathy associated with selective necrosis of medullary thick ascending limbs. In brief, rats were administered radiocontrast medium or vehicle injections for controls after combined inhibition of prostanoids and nitric oxide. Twenty-four hours after the insult, tissue mRNAs for IGF-I, the IGF-I receptor, and IGF-binding proteins (IGFBP) 1 and 3 were assayed in cortex, medulla, and liver by solution hybridization-RNase protection assay, and IGFBPs were measured in serum and tissue by Western ligand blotting. Cortical IGF-1 increased, whereas medullary IGF-I mRNA decreased. Renal IGFBPs decreased, whereas IGFBP-1 mRNA increased. The IGF system in the liver was unchanged. We conclude that general changes in renal IGFBPs in this experimental model of acute renal failure might increase the level of cortical IGF-I in a way that could modulate medullary recovery.

Acute Kidney Injury↗
PubMed1998

Systemic administration of epidermal growth factor reduces fat mass in rats: effects on the hormone-sensitive-lipase, lipoprotein lipase and leptin.

We examined whether the reduction in fat mass induced by EGF treatment in mature animals was via activation of hormone-sensitive lipase (HSL) and thereby the induction of lipolysis, or through inhibition of lipoprotein lipase activity thus reducing fat uptake in adipose tissue. Sixteen male rats were treated with placebo or EGF 150 microg/kg/day for 7 days via mini-osmotic pumps. The results demonstrate that systemic EGF treatment reduces the amount of adipose tissue, most likely due to increased lipolysis as HSL activity as well as HSL mRNA were increased. The circulating levels of free fatty acids were slightly increased and leptin levels reflected the decrease in adipose tissue mass.

Adipose Tissue↗
PubMed1998

Developmental changes in serum levels of free and total insulin-like growth factor I (IGF-I), IGF-binding protein-1 and -3, and the acid-labile subunit in rats.

We have recently described a competitive binding assay for rat insulin-like growth factor-binding protein-3 (IGFBP-3) based on the ability of IGFBP-3 to form a ternary complex with the acid-labile subunit (ALS) in the presence of IGF-I. Using this assay we studied groups of male (n = 6) and female rats (n = 6) at 20, 30, 40, 50, 60, 80, and 130 days of age. Nonfasting serum levels of IGFBP-3 were compared with those of total (extractable) IGF-I (tIGF-I) and ALS as well as IGFBP-3 determined by ligand blotting. Additionally, we studied the relationship between ultrafiltered free IGF-I (fIGF-I) and immunoassayable IGFBP-1. IGFBP-3 was dependent on age only (P < 0.0001), but tended to be higher in males than in females (P = 0.06); between 20-130 days levels increased from 6.5 +/- 1.7 to 73.6 +/- 7.2 nmol/liter in males and from 5.4 +/- 1.6 to 51.3 +/- 8.0 nmol/liter in females. IGFBP-3 correlated positively with tIGF-I (r = 0.90; P < 0.0001), ALS (r = 0.92; P < 0.0001), and IGFBP-3, as determined by ligand blotting (r = 0.88; P < 0.0001). The molar ratio of IGFBP-3 to tIGF-I increased from 0.23 +/- 0.04 to 0.76 +/- 0.04 (P < 0.0001) without any sex dependence. An age- and sex-dependent decrease in IGFBP-1 was observed (P < 0.0001), from 10.9 +/- 2.5 to 1.2 +/- 0.2 nmol/liter in females and from 8.9 +/- 0.7 to 0.2 +/- 0.04 nmol/liter in males. Free IGF-I (fIGF-I) increased with age (from 0.7 +/- 0.2 to 7.1 +/- 0.5 nmol/liter; P < 0.0001), and levels were inversely correlated with IGFBP-1 (r = -0.80; P < 0.0001). In young rats, IGFBP-1 circulated in a 10-fold molar excess over the level of fIGF-I, whereas in older rats, fIGF-I exceeded IGFBP-1 by an average of 9-fold in females and by up to almost 60-fold in males. We conclude that in rats 1) IGFBP-3 and fIGF-I are strongly age dependent; 2) IGFBP-3 correlates positively with ALS and tIGF-I; and 3) fIGF-I and IGFBP-1 are inversely correlated. This is in accordance with clinical findings. However, in humans the adult level of fIGF-I rarely exceeds 0.3 nmol/liter, and IGFBP-1 usually circulates in excess of fIGF-I. Thus, our results also imply species differences in the IGF systems of humans and rats.

Age Factors↗
PubMed1998

No effect of growth hormone on serum insulin-like growth factor binding protein-3 proteolysis.

Increased proteolysis of insulin-like growth factor binding protein (IGFBP)-3 is seen in several pathophysiological conditions and may represent an important mechanism for the regulation of insulin-like growth factor bioavailability. It has previously been suggested that proteolysis of IGFBP-3 is dependent on the GH status. To investigate this, IGFBP-3 proteolysis was measured in three groups of subjects: 1) GH-deficient patients before and after GH replacement (n = 14); 2) healthy subjects before and after 14 days of GH administration (n = 7); and 3) acromegalic patients before and after treatment with a long-acting SRIH analogue (octreotide; n = 14). In vivo IGFBP-3 proteolysis was investigated by Western immunoblotting. No difference was detected in pretreatment samples, and GH treatment in GH-deficient subjects or octreotide treatment in acromegalic subjects had no impact on in vivo proteolysis. In contrast, GH administration to healthy subjects caused a 21% increase in in vivo proteolysis (P = 0.0008). In vitro IGFBP-3 proteolysis was investigated by incubation of serum with 125I-rhIGFBP-3, followed by SDS-PAGE. In pretreatment samples, the percentage of proteolyzed 125I-rhIGFBP-3 was 13 +/- 1% (acromegalic subjects), 11 +/- 1% (healthy subjects), and 9 +/- 1% (GH-deficient subjects) (P < 0.009, GH-deficient vs. acromegalic subjects). Treatment had no effect on in vitro proteolysis. We conclude that GH status has no major impact on IGFBP-3 protease activity in serum.

Acromegaly↗
PubMed1998

Differential changes in free and total insulin-like growth factor I after major, elective abdominal surgery: the possible role of insulin-like growth factor-binding protein-3 proteolysis.

Major surgery is accompanied by extensive proteolysis of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3). Proteolysis of IGFBP-3 is generally believed to increase IGF bioavailability due to a diminished affinity of the IGFBP-3 fragments for IGFs. We have investigated 18 patients undergoing elective ileo-anal J-pouch surgery. Patients were randomized to treatment with GH (12 IU/day; n = 9) or placebo (n = 9) from 2 days before to 7 days after operation. Free IGF-I and IGF-II were measured by ultrafiltration of serum, and IGFBP-3 proteolytic activity was determined by a [125I]recombinant human IGFBP-3 degradation assay. In the GH-treated group, total IGF-I increased preoperatively by 99%. Postoperatively, total IGF-I decreased by 48% (placebo) and 52% (GH). Immunoassayable IGFBP-3 decreased by 27% (placebo) and 26% (GH). In the placebo-treated group, free IGF-I was unchanged throughout the study. In the GH-treated group, free IGF-I increased by 277% preoperatively and remained elevated after operation. IGFBP-3 proteolytic activity increased by 63-73% after operation. The relative elevations of free IGF-I levels despite decreased total IGF-I levels could thus relate to augmented IGFBP-3 proteolysis.

Adult↗