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Biomedical subjects

Allan Flyvbjerg

Publications and source records attributed to Allan Flyvbjerg.

At least 55 records · Page 3Linked to original sources
PubMed2005

Effects of 2 wk of GH administration on 24-h indirect calorimetry in young, healthy, lean men.

The present study was designed as a randomized, double-blind placebo (Plc)-controlled study to determine the effect of 2 wk of growth hormone administration (GH-adm.) on energy expenditure (EE) and substrate oxidation in healthy humans. Sixteen young healthy men were divided into two groups. The study consisted of two 24-h measurements (indirect calorimetry), separated by 2 wk of either Plc or GH injections (6 IU/day). At baseline, no significant differences were observed between the two groups in any of the measured anthropometric, hormonal, or metabolic parameters, neither did the parameters change over time in the Plc group. GH-adm. resulted in a 4.4% increase in 24-h EE (P < 0.05) and an increase in fat oxidation by 29% (P < 0.05). However, a decrease in the respiratory quotient was only observed in the postabsorptive phase after an overnight fast (0.84 +/- 0.1 to 0.79 +/- 0.1, P < 0.05). Furthermore, lean body mass (LBM) was increased by GH-adm. only [62.8 +/- 2.5 kg (baseline) vs. 64.7 +/- 2.4 kg (after), P < 0.001]. In conclusion, GH-adm. increases 24-h EE, which may be partly explained by increased LBM. Furthermore, GH-adm. stimulates fat combustion, especially in the postabsorptive state.

Adult↗
PubMed2005

No effect of growth hormone administration on substrate oxidation during exercise in young, lean men.

The purpose of this study was to examine the effects of increased fat availability induced by growth hormone (GH) administration on the oxidative metabolism during exercise. Seven well-trained males (age 25 +/- 2 years (mean +/- S.E.M.); peak oxygen consumption : 62 +/- 1 ml min(-1) kg(-1) (completed four randomised trials: 120 min bicycling at 55% 4 h after receiving either 7.5 IU (2.5 mg) GH or placebo (Plc), and during rest after receiving either GH or Plc. In all studies a standardized meal was given 2 h after GH or Plc injection. GH administration resulted in an approximately 60-fold increase in serum GH concentration at rest (P < 0.0001) and during exercise (P < 0.0001). The increase in serum GH was followed by an increase in circulating glycerol at rest (8%, P < 0.0001). When combined with exercise the increase in plasma glycerol was more pronounced (GH: 716% of baseline versus Plc: 328%, P < 0.0001). However, this increase in fat mobilization did not increase fat oxidation during exercise (indirect calorimetry). In conclusion, GH administration combined with aerobic exercise increased lipolytic parameters substantially more than exercise alone, but did not further augment whole body fat oxidation.

Adipose Tissue↗
PubMed2005

Coordinated collagen and muscle protein synthesis in human patella tendon and quadriceps muscle after exercise.

We hypothesized that an acute bout of strenuous, non-damaging exercise would increase rates of protein synthesis of collagen in tendon and skeletal muscle but these would be less than those of muscle myofibrillar and sarcoplasmic proteins. Two groups (n = 8 and 6) of healthy young men were studied over 72 h after 1 h of one-legged kicking exercise at 67% of maximum workload (W(max)). To label tissue proteins in muscle and tendon primed, constant infusions of [1-(13)C]leucine or [1-(13)C]valine and flooding doses of [(15)N] or [(13)C]proline were given intravenously, with estimation of labelling in target proteins by gas chromatography-mass spectrometry. Patellar tendon and quadriceps biopsies were taken in exercised and rested legs at 6, 24, 42 or 48 and 72 h after exercise. The fractional synthetic rates of all proteins were elevated at 6 h and rose rapidly to peak at 24 h post exercise (tendon collagen (0.077% h(-1)), muscle collagen (0.054% h(-1)), myofibrillar protein (0.121% h(-1)), and sarcoplasmic protein (0.134% h(-1))). The rates decreased toward basal values by 72 h although rates of tendon collagen and myofibrillar protein synthesis remained elevated. There was no tissue damage of muscle visible on histological evaluation. Neither tissue microdialysate nor serum concentrations of IGF-I and IGF binding proteins (IGFBP-3 and IGFBP-4) or procollagen type I N-terminal propeptide changed from resting values. Thus, there is a rapid increase in collagen synthesis after strenuous exercise in human tendon and muscle. The similar time course of changes of protein synthetic rates in different cell types supports the idea of coordinated musculotendinous adaptation.

Adult↗
PubMed2005

Pathophysiological role of vascular endothelial growth factor in the remnant kidney.

BACKGROUND: Subtotal renal ablation is characterized by initial glomerular hypertrophy, followed by progressive development of glomerulosclerosis and interstitial fibrosis. Vascular endothelial growth factor (VEGF) is involved in glomerular hypertrophy and dysfunction in several pathophysiological conditions. On the other hand, progressive glomerulosclerosis and tubulo-interstitial fibrosis in the remnant kidney have been associated with loss of VEGF expression. METHODS: To explore the pathophysiological role of VEGF in the development of glomerular hypertrophy and renal damage in the remnant kidney model, we examined the effect of a neutralizing VEGF antibody on glomerular volume and kidney function in rats after subtotal nephrectomy or sham operation. Erythropoietin was administered to exclude a confounding effect of anaemia. RESULTS: Six weeks after subtotal nephrectomy, plasma urea and creatinine concentrations, urinary albumin excretion, and mean glomerular volume were elevated in the placebo-treated uraemic rats as compared with the sham-operated rats. Inhibition of VEGF partially prevented the glomerular hypertrophy and largely prevented the rise in urinary albumin excretion, but did not affect creatinine clearance in uraemic rats. CONCLUSIONS: VEGF is a mediator of glomerular hypertrophy after subtotal renal ablation. In view of glomerular hypertrophy as the initial deleterious event ultimately leading to progressive glomerulosclerosis, agents that block this glomerular growth could be useful in preventing scarring in progressive renal disease.

Animals↗
PubMed2005

Complement activation and diabetic vascular complications.

Diabetes mellitus is a major and increasing health problem worldwide. One of the most serious consequences of diabetes is the development of diabetic angiopathy, which includes cardiovascular disease, neuropathy, retinopathy and nephropathy. Diabetic nephropathy alone affects 15-25% of patients with type 1 diabetes and 30-40% of patients with type 2 diabetes and is the single-most important cause of end-stage renal failure in the Western World. Existing research has demonstrated the involvement of glycation factors, growth factors/cytokines, hemodynamic factors and intracellular changes in the pathogenesis of diabetic kidney disease. An emerging amount of recent data suggests that the complement system, especially the MBL pathway, plays an important role in the pathogenesis of diabetic vascular complications. Although the numerous therapeutic interventions available today may delay the development and progression of diabetes vascular complications, there is an ongoing need for new therapeutic strategies. In this article the evidence for a connection between the complement system and vascular dysfunction will be reviewed, with a special focus on the relation to diabetic kidney disease. Several ways of specifically manipulating the complement system already exist. However, whether or not these drugs provide new targets for intervention on diabetic vascular complications is still unknown.

Animals↗
PubMed2005

Growth hormone binding protein and maternal body mass index in relation to placental growth hormone and insulin requirements during pregnancy in type 1 diabetic women.

In pregnancy, the growth hormone axis is shifted from pituitary growth hormone (GH) to placental growth hormone (PGH). Their common binding protein, GH binding protein (GHBP), displays peak serum levels at mid-gestation in normal individuals. In the non-pregnant state, diabetes is known to be associated with elevated levels of GH and decreased levels of insulin-like growth factors (IGFs) and GHBP. Diabetes in pregnancy may therefore as well be associated with disturbances in the growth hormone axis. In the present study, we aimed at investigating the impact of GHBP and maternal body mass index (BMI) on levels of PGH, thereby enabling estimation of any association between free PGH and weight adjusted insulin requirements. In 51 type 1 diabetic women, blood samples were collected in gestational week 10+, 16+, 22+, 28+ and 34+, and analysed for their serum content of GHBP, PGH, and GH. Serum GHBP increased from the first weeks of pregnancy to median 2.07 nmol/l (range 1.17-4.26) in week 22+, then declined to median 1.29 nmol/l (range 0.77-2.35) in week 34+ (ANOVA P < 0.001). Serum PGH levels were highest in week 34+ at median 21.3 microg/l (range 5.1-165.4) (P < 0.001), whereas a steady decrease in GH values was observed throughout pregnancy to a median 0.17 microg/l (range 0-5.53). The fraction of calculated free PGH to total PGH increased from mid-gestation onwards to 55.2% (37.0-87.1) in week 34+ at a median level of free PGH of 10.4 microg/l (range 1.9-144.0) (P < 0.001). Similarly, the molar ratio of total PGH to GHBP increased to a maximum of 0.68 (0.12-6.62) in week 34+. As in normal pregnancies, the correlation between BMI and GHBP was lost in late pregnancy. The newborns birth weight z-score correlated with total PGH and derivatives here-of in week 34+. Neither total nor weight adjusted insulin requirements correlated to total PGH, calculated free PGH, nor GHBP. In conclusion, PGH and GHBP display a similar course during pregnancy in type 1 diabetic women as described in normal women. The well-known association between GHBP and BMI was lost in late pregnancy. Calculated levels of free PGH were positively associated to fetal growth, but not to maternal insulin requirements.

Adult↗
PubMed2005

The IGF-system is not affected by a twofold change in protein intake in patients with type 1 diabetes.

OBJECTIVE: In type 1 diabetes the circulating IGF-system is altered with low IGF-I and changes in levels of IGF-binding proteins (IGFBPs) which may be of importance for the development of diabetes complications. Our aim was to study if IGF-I, as supported by experimental data in animals, can be affected by dietary protein intake. DESIGN AND METHODS: Twelve patients with type 1 diabetes, age 37.5+/-10.0 years (mean+/-SD), diabetes duration 20.1+/-9.3 years and HbA1c 6.3+/-0.6% were allocated to isocaloric diets with either low normal protein content (LNP), (10 E%; 0.9 g protein/kg body weight) or high normal protein content (HNP) (20 E%; 1.8 g protein/kg body weight) in an open randomised cross-over study. Each diet was taken for 10 days with a wash-out period of 11 days in between. Circulating levels of total and free IGF-I and -II, IGFBP-1, -2 and -3 and GH-binding protein (GHBP) as well as ghrelin were measured with validated in-house immunoassays. RESULTS: At day 10, urinary urea excretion was 320+/-75 mmol/24h during LNP diet compared with 654+/-159 mmol/24h during HNP diet (p<0.001). There were no changes in body weight or glycaemic control between the diets. Fasting levels of total IGF-I were 121+/-33 microg/L after LNP and 117+/-28 microg/L after HNP diet (ns) and the corresponding concentrations of IGFBP-1 were 142(141) and 132(157)mug/L [median (IQR)] (ns). There were no differences in plasma concentrations of total IGF-II, free IGF-I and -II, IGFBP-3, GHBP and ghrelin, whereas a small difference was found for IGFBP-2 (302+/-97 vs. 263+/-66 microg/L; LNP vs. HNP; p<0.04). CONCLUSIONS: A twofold change of the dietary protein intake does not influence the altered circulating IGF-system in type 1 diabetes. In order to affect the IGF-system other interventions must be used.

Adult↗
PubMed2005

Insulin-like growth factor I (IGF-I) replacement therapy increases albumin concentration in liver cirrhosis: results of a pilot randomized controlled clinical trial.

BACKGROUND/AIMS: Insulin-like growth factor I (IGF-I) is an anabolic hormone synthesized in the liver whose levels decrease sharply in liver cirrhosis. METHODS: We conducted a randomized double-blind placebo-controlled clinical trial to evaluate the effect of subcutaneous administration of IGF-I (20 microg/kg/day with dose escalation to 50-100 microg/kg/day) for 4 months in patients with alcoholic or primary biliary cirrhosis (PBC) and subnormal IGF-I levels. Eight alcoholics and one PBC entered the placebo group and seven alcoholics and two PBC the treatment group. Biochemistry, body composition, muscle mass and strength, and resting energy expenditure (REE) were evaluated. RESULTS: Total serum IGF-I and IGF-I/IGFBP-3 ratio (a surrogate marker of IGF-I biovailability) increased in the treatment group but IGF-I values still remained below normal limits in the treated patients. No differences were observed in body composition, muscle strength or muscle mass between groups. However, IGF-I therapy increased significantly serum albumin (P = 0.038) and this improvement correlated positively with variation of IGF-I/IGFBP-3 ratio. IGF-I treatment also tended to increase REE (P = 0.085); this difference was significant (P = 0.049) in the subgroup of alcoholic patients. CONCLUSIONS: A short course of IGF-I increased albumin levels and tended to improve energy metabolism in liver cirrhosis. These findings warrant larger clinical trials to assess the clinical benefit of IGF-I in cirrhotic patients.

Adult↗
PubMed2005

Insulin-like growth factors (IGFs) and IGF binding proteins in active Crohn's disease treated with omega-3 or omega-6 fatty acids and corticosteroids.

OBJECTIVE: Catabolism and growth impairment are well-known complications of inflammatory bowel disease (IBD). This may be caused by the disease activity itself and/or the medical treatment, and both may lead to changes in the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis. The aim of the present study was to examine the effects of enteral nutrition, Impact Powder, as adjuvant therapy to corticosteroid treatment on changes in the GH/IGF-I axis in patients with Crohn's disease (CD). MATERIAL AND METHODS: The patients were randomized to 3-IP (omega-3-fatty acid (FA), 3 g/day) or 6-IP (omega-6-FA, 9 g/day). Changes in total IGF-I (tIGF-I) and total IGF-II (tIGF-II), free IGF-I (fIGF-I), IGF binding proteins (IGFBP-1 and IGFBP-3), IGFBP-3 protease activity and insulin levels were examined in 31 patients with active CD (CDAI: 186-603) during treatment with prednisolone (40 mg for 1 week) and tapering the dose by 5 mg/week. Clinical and biochemical markers of inflammation were studied at day 0, and after 5 and 9 weeks. RESULTS: There were no differences at baseline between the two groups. During the treatment period, tIGF-I, fIGF-I and IGFBP-3 increased significantly in both groups compared to baseline (p<0.05) without differences between the groups. Insulin and IGFBP-1 showed no significant changes throughout the treatment period. CONCLUSIONS: There was no difference between 3-IP and 6-IP as adjuvant enteral nutrition on the GH/IGF-I axis. The changes observed in the GH/IGF-I axis are in line with previously published studies and may be explained by corticosteroid treatment; however, we cannot exclude an additional effect of omega3-/omega6 FA as adjuvant enteral nutrition.

Adolescent↗
PubMed2005

Ghrelin and its relationship to growth hormones during normal pregnancy.

OBJECTIVE: Ghrelin and GH secretagogue receptors have been found in reproductive organs, including the placenta. The physiology of ghrelin in pregnancy has not been explored. In human pregnancy, pituitary GH is gradually replaced by placental GH (PGH). The present study was undertaken to examine serum ghrelin levels during normal pregnancy and to determine to what extent changes in ghrelin levels coincide with changes in serum levels of free and total GH and PGH. Design Prospective study with blood sampling from pregnant women in gestational weeks 8, 18, 26 and 36 and postpartum. PATIENTS: Eleven nondiabetic pregnant women with singleton pregnancies. MEASUREMENTS: Serum ghrelin was determined using an in-house radioimmunoassay. Serum PGH was determined in a solid-phase immunoradiometric assay, serum GH and insulin in a time-resolved immunofluorometric assay, and serum GHBP in an in-house immunofunctional assay. RESULTS: Serum ghrelin levels peaked in week 18 (1.20 +/- 0.09 microg/l) and the lowest levels were observed in late third trimester (0.87 +/- 0.06 microg/l), corresponding to a mean decrease of 27.7% (P < 0.001) from peak levels. An increase was observed again postpartum. Serum GH diminished throughout pregnancy to low third-trimester values (0.12 +/- 0.03 microg/l; P < 0.001), and PGH increased to 25.7 +/- 2.86 microg/l (P < 0.001) in week 36. Neither total nor calculated free levels of growth hormones correlated to ghrelin levels, and no significant correlations were observed between ghrelin and maternal body mass index (BMI) or fasting insulin levels. CONCLUSIONS: Serum ghrelin levels peak around mid-gestation in human pregnancy. Ghrelin levels during pregnancy are at their lowest in the third trimester at a time of increased body weight, development of insulin resistance and high serum levels of PGH. However, no associations were observed between ghrelin and the two growth hormones.

Adult↗
PubMed2005

Kidney growth in normal and diabetic mice is not affected by human insulin-like growth factor binding protein-1 administration.

Insulin-like growth factor I (IGF-I) accumulates in the kidney following the onset of diabetes, initiating diabetic renal hypertrophy. Increased renal IGF-I protein content, which is not reflected in messenger RNA (mRNA) levels, suggests that renal IGF-I accumulation is due to sequestration of circulating IGF-I rather than to local synthesis. It has been suggested that IGF-I is trapped in the kidney by IGF binding protein 1 (IGFBP-1). We administered purified human IGFBP-1 (hIGFBP-1) to nondiabetic and diabetic mice as three daily sc injections for 14 days, starting 6 days after induction of streptozotocin diabetes when the animals were overtly diabetic. Markers of early diabetic renal changes (i.e., increased kidney weight, glomerular volume, and albuminuria) coincided with accumulation of renal cortical IGF-I despite decreased mRNA levels in 20-day diabetic mice. Human IGFBP-1 administration had no effect on increased kidney weight or albuminuria in early diabetes, although it abolished renal cortical IGF-I accumulation and glomerular hypertrophy in diabetic mice. Increased IGF-I levels in kidneys of normal mice receiving hIGFBP-1 were not reflected on kidney parameters. IGFBP-1 administration in diabetic mice had only minor effects on diabetic renal changes. Accordingly, these results did not support the hypothesis that IGFBP-1 plays a major role in early renal changes in diabetes.

Animals↗
PubMed2005

Pro- and mature IGF-II during diet-induced weight loss in obese subjects.

BACKGROUND: In normal subjects up to 10% of circulating insulin-like growth factor II (IGF-II) consists of pro-IGF-II. However, its regulation and biological impact remains unknown. In obese subjects, serum free and total IGF-II are increased, and we therefore investigated the impact of obesity and diet on serum pro-IGF-II. DESIGN: Non-diabetic, obese subjects (n = 34) with a body mass index (BMI) of 38.9 +/- 0.5 kg/m2 were subjected to 8 weeks with very low calorie diet (800 kcal/day) followed by 12 weeks with a weight-stabilizing diet. Fasting serum was collected before the study, and after 8 and 20 weeks. Pro-IGF-II was determined after acid-gel chromatography using a novel, highly specific in-house assay, free and total IGFs were measured after ultrafiltration and acid-ethanol extraction, respectively, and IGF-binding proteins (IGFBPs) were measured with specific immunoassays. RESULTS: Diet reduced BMI and fasting levels of insulin and glucose (P < 0.001). Serum pro-IGF-II was markedly reduced in obese subjects as compared with matched normal-weight controls (means and 95% confidence intervals: 93 microg/l (82-104 microg/l) versus 171 microg/l (152-192 microg/l), respectively; P < 0.001), and levels remained unchanged after the weight loss. In contrast, during the study period total and free IGF-II decreased (P < 0.05), whereas total IGF-I, IGFBP-1 and IGFBP-2 increased (P < 0.001). Serum free IGF-I remained unaltered. Cross-sectional and longitudinal correlation analyses showed that pro-IGF-II was closer and more consistently associated with IGF-I than IGF-II. CONCLUSION: This study demonstrates that pro-IGF-II is reduced in obesity, in contrast to mature IGF-II. This indicates a hitherto unrecognized link between nutrition and pro-IGF-II. In addition, our data indicate that pro-IGF-II is regulated independently of mature IGF-II.

Adult↗
PubMed2005

Long-term AICAR administration and exercise prevents diabetes in ZDF rats.

Lifestyle interventions including exercise programs are cornerstones in the prevention of obesity-related diabetes. The AMP-activated protein kinase (AMPK) has been proposed to be responsible for many of the beneficial effects of exercise on glucose and lipid metabolism. The effects of long-term exercise training or 5-aminoimidazole-4-carboxamide-1-beta-d-riboruranoside (AICAR) treatment, both known AMPK activators, on the development of diabetes in male Zucker diabetic fatty (ZDF) rats were examined. Five-week-old, pre-diabetic ZDF rats underwent daily treadmill running or AICAR treatment over an 8-week period and were compared with an untreated group. In contrast to the untreated, both the exercised and AICAR-treated rats did not develop hyperglycemia during the intervention period. Whole-body insulin sensitivity, as assessed by a hyperinsulinemic-euglycemic clamp at the end of the intervention period, was markedly increased in the exercised and AICAR-treated animals compared with the untreated ZDF rats (P < 0.01). In addition, pancreatic beta-cell morphology was almost normal in the exercised and AICAR-treated animals, indicating that chronic AMPK activation in vivo might preserve beta-cell function. Our results suggest that activation of AMPK may represent a therapeutic approach to improve insulin action and prevent a decrease in beta-cell function associated with type 2 diabetes.

AMP-Activated Protein Kinases↗
PubMed2005

Mannose-binding lectin as a predictor of microalbuminuria in type 1 diabetes: an inception cohort study.

Inflammation and complement activation via the mannose-binding lectin (MBL) pathway have been suggested to play a role in the pathogenesis of diabetic microvascular complications. The association between the complement-activating protein MBL and the development of persistent microalbuminuria was evaluated in an inception cohort of 286 newly diagnosed type 1 diabetic patients consecutively admitted to the Steno Diabetes Center between 1 September 1979 and 31 August 1984. Serum MBL was measured with an immunofluorometric assay in 270 of the patients (159 men) after 3 years of diabetes duration. During the median (range) follow-up period of 18.0 (1.0-21.8) years, 75 patients subsequently progressed to persistent micro- or macroalbuminuria (urinary albumin excretion rate >30 mg/24 h). In patients with MBL levels above the median (1,597 microg/l), the cumulative incidence of persistent micro- or macroalbuminuria was 41% (CI 31-50) as compared with 26% (CI 17-34) in patients with MBL levels below the median (log-rank test, P = 0.003). In a Cox proportional hazard model with sex and age as fixed covariates, MBL was independently associated with later development of persistent micro- or macroalbuminuria (hazard ratio 1.21 [CI 1.02-1.42] per 1,000 microg/l increase in MBL; P = 0.03) after adjusting for possible confounders. In our study, high levels of MBL early in the course of type 1 diabetes was significantly associated with later development of persistent micro- or macroalbuminuria, suggesting that complement activation initiated by MBL may be involved in the pathogenesis of diabetic microvascular complications.

Adult↗
PubMed2005

Serum adiponectin is increased in type 1 diabetic patients with nephropathy.

OBJECTIVE: To elucidate whether serum adiponectin is associated with renal function, low-grade inflammatory markers, metabolic control, and insulin resistance in type 1 diabetic patients with and without nephropathy. RESEARCH DESIGN AND METHODS: A total of 189 type 1 diabetic patients from the Finnish Diabetic Nephropathy Study were divided into three groups based on their urinary albumin excretion rate (AER): patients with normal AER (n = 66) had no antihypertensive medication, while patients with microalbuminuria (n = 63) or macroalbuminuria (n = 60) were all treated with an ACE inhibitor. Renal function was estimated with the Cockcroft-Gault formula. Adiponectin was measured by an in-house time-resolved immunofluorometric assay. RESULTS: Adiponectin concentrations were higher in women than in men, but since there was no significant difference in sex distribution between the groups, data were pooled. Adiponectin concentrations were higher in patients with macroalbuminuria (19.8 +/- 12.0 mg/l) than in patients with microalbuminuria (13.1 +/- 4.8 mg/l) or normoalbuminuria (11.8 +/- 4.2 mg/l). In a univariate analysis, adiponectin was positively associated with creatinine (r = 0.41; P < 0.0001), AER (r = 0.33; P < 0.0001), interleukin-6 (r = 0.22; P = 0.002), systolic blood pressure (r = 0.22; P = 0.004), HbA(1c) (r = 0.17; P = 0.02), total cholesterol (r = 0.16; P = 0.03), and HDL cholesterol (r = 0.16; P = 0.03) and negatively with estimated glomerular filtration rate (GFR; r = -0.52; P < 0.0001) and waist-to-hip ratio (WHR; r = -0.16; P = 0.03). In a multiple linear regression analysis including the above variables, estimated GFR, AER, and WHR were independently associated with adiponectin levels (r(2) = 0.32). CONCLUSIONS: Serum adiponectin concentrations are increased in type 1 diabetic patients with nephropathy, and levels are further associated with renal insufficiency.

Adiponectin↗
PubMed2004

Free IGF-I, IGFBP-1, and the binary complex of IGFBP-1 and IGF-I are increased during human pregnancy.

BACKGROUND/AIMS: To investigate changes in free insulin-like growth factor I (IGF-I) and IGF-binding protein 1 (IGFBP-1) complexed IGF-I during human pregnancy. METHODS: Overnight fasting serum was obtained in a longitudinal design from 11 women with non-complicated pregnancy at gestation weeks 6-10, 16-20, 24-28 and 35-38 and, for comparison, 5 weeks post-partum. All samples were analyzed for total and free IGF-I and IGF-II, IGFBP-3 and IGFBP-3 proteolysis, total and non-phosphorylated (np-) IGFBP-1, and IGFBP-1 complexed IGF-I. RESULTS: Total IGF-I was increased in late pregnancy (week 35-38) (p < 0.001), whereas free IGF-I was significantly increased by 77% already at week 6-10 (p = 0.004) and by 140% (p = 0.002) at week 34-38, when compared to post-partum levels. At weeks 16-20 and 24-28, levels of free IGF-I were not significantly different from post-partum levels. Significant IGFBP-3 proteolysis was detectable from week 6-10 and throughout pregnancy (p < 0.05). Total and np-IGFBP-1 were significantly increased from 16-20 weeks of pregnancy (both p < 0.05) and IGFBP-1 complexed IGF-I was increased 2-fold from week 16-20 and throughout pregnancy (p < 0.05). However, the saturation of IGFBP-1 remained constant at 27-29% during the study. CONCLUSION: We found evidence of increased free IGF-I and increased IGF-I in binary complexes during pregnancy, possibly caused by IGFBP-3 proteolysis and decreased ternary complex formation.

Adult↗
PubMed2004

Administration of human insulin-like growth factor-binding protein-1 increases circulating levels of growth hormone in mice.

GH is the major regulator of circulating IGF-I, which, in return, controls pituitary GH secretion by negative feedback. IGF-binding protein-1 (IGFBP-1) is believed to modify this feedback through its effects on free IGF-I. In the present study we investigated the potential influence of IGFBP-1 on GH secretion in the absence or presence of a GH receptor antagonist (GHRA) that specifically blocks peripheral GH action. We administered human (h) IGFBP-1 and GHRA to mice alone or in combination for 2 or 7 d. GHRA was administered in a dose previously shown to block GH action without an effect on circulating GH or IGF-I levels. hIGFBP-1 administration increased stimulated circulating GH levels and serum total IGF-I and IGFBP-3 levels. Coadministration of GHRA abolished the hIGFBP-1-induced increase in serum IGF-I and IGFBP-3 levels, whereas stimulated GH levels remained increased. Free IGF-I levels in serum were unchanged in all treatment groups. In conclusion, GH serum levels increased in response to hIGFBP-1 administration, even in the setting of normal IGF-I levels. This finding suggests a direct involvement of IGFBP-1 in GH secretion.

Animals↗