Postpartum nutrition affects the insulin-like growth factor system in dominant follicles and plasma of anestrous beef cows.

Effects of nutrition on insulin-like growth factor-I (IGF-I), IGF binding proteins (IGFBP), and insulin in plasma and dominant follicles were evaluated at day 72 and 56 (Exp. 1, n = 12 and Exp. 2, n = 28, respectively) postpartum in anovulatory primiparous beef cows. Cows were stratified based on body condition score at calving and randomly assigned to nutritional treatments: maintain (M), 2.27 kg of a 40 % CP supplement per day and ad libitum hay; or gain (G), ad libitum access to a 50 % concentrate diet and ad libitum hay. Blood samples were collected twice weekly starting 30 days postpartum. Ovarian follicles were evaluated using ultrasonography commencing 42 (Exp. 1) or 30 (Exp. 2) days postpartum. Body weight and condition score were greater (P < 0.05) for cows of G than M groups and postpartum interval to luteal function was longer for cows of the M than G group. Insulin and IGF-I concentrations in follicular fluid (FF) and plasma were greater (P < 0.05) for cows of the G than M group at follicular aspiration. Plasma and FF IGFBP4 and IGFBP5 concentrations were greater (P <  0.05) in Exp. 2, and IGFBP5 was greater in Exp. 1 for cows of the G than M group. Treatment did not affect FF steroid concentrations or granulosal cell CYP19A1, PAPPA, IGFBP4, and IGFBP5 mRNA abundance. These results indicate concentrations of IGF-I, insulin, IGFBP4, and IGFBP5 in FF and plasma are affected by nutritional intake and may be related to follicular function.

IGF and IGFBP as an index for discrimination between vitamin D supplementation responders and nonresponders in overweight Saudi subjects.

Vitamin D deficiency is common in the Kingdom of Saudi Arabia (KSA). Therefore, it is significant to recognize which biochemical markers modulate serum 25 hydroxyvitamin D (25(OH)D) in response to vitamin D supplementation in such a population. Our aim was to study the correlation of insulin-like growth factor (IGF) and insulin growth factor binding protein (IGFBP) with serum 25(OH)D in response to vitamin D supplementation in a Saudi population. A total of 199 (89 males/110 females) vitamin D deficient subjects (25(OH)D level <50 nmol/L), aged 40.4 ±â€Š11.4 years, were given vitamin D supplements (50,000 IU/mL every week) for the first 2 months, then twice a month for 2 months, followed by daily 1000 IU in the last 2 months. Fasting blood samples were taken at baseline and 6 months after the final dose of vitamin D. Serum 25(OH)D, IGF-1 and IGF-2, and IGFBPs 2-5 were measured. Vitamin D response was computed for all subjects as the difference in levels of serum 25(OH)D concentration at the end of 6 months compared to baseline. After intervention, serum 25(OH)D concentration significantly increased from 35.6 nmol/L (26.6-43.5) to 61.8 nmol/L (54.8-73.3) in responder subjects (P < .01) and from 35.1 nmol/L (21.2-58.2) to 38.3 nmol/L (25.5-48.3) in nonresponders (P = .13). Subjects with lower baseline serum IGF-II, IGFBP-2, and IGF-1/IGFBP-3 ratio are more sensitive to acute vitamin D status changes. IGF1 and IGF-1/IGFBP-3 ratio significantly increased in all subjects after 6 months (P = .01). Changes in 25(OH)D was significantly associated with changes in IGFBP-2 and IGF-1/IGFBP-3 ratio in responders only. This study proposes that changes in circulating IGF-I and IGFBP-3 are modulated by vitamin D supplementation and can be taken into consideration in investigations involving vitamin D correction. Moreover, increase in serum 25(OH)D and IGF-I/IGFBP-3 molar ratio are more sensitive markers for the response to vitamin D supplementation in Saudi population.

The effect of HMB ingestion on the IGF-I and IGF binding protein response to high intensity military training.

OBJECTIVE: Insulin-like growth factor-I (IGF-I) is a metabolic and anabolic biomarker that has been proposed to reflect physiological adaptations resulting from multistressor environments. The bioactivity of IGF-I is regulated by seven different insulin-like growth factor binding proteins (IGFBPs) which act not only as carriers of IGF-1, but also function as a modulator of IGF-I availability and activity. Supplementing with ß-hydroxy-ß-methylbutyrate (HMB) has been shown to enhance physiological outcomes associated with intense training, and has been reported to augment the IGF-1 response. The purpose of this study was to examine the effect of 23days of HMB supplementation on circulating levels of IGF-I and IGFBPs in combat soldiers during highly intense military training. METHODS: Thirteen male soldiers from an elite infantry unit volunteered to participate in this double-blind, parallel design study. Soldiers were provided 3g·day-1 of either HMB (n=6) or placebo (PL; n=7). During the study soldiers performed advanced military training with periods of restricted sleep and severe environmental stressors. Blood samples were obtained prior to (PRE) and approximately 18h following the final supplement consumption (POST). RESULTS: No significant differences were observed for circulating IGF-1 concentrations between HMB and PL (p=0.568). In addition, no differences were seen between the groups for IGFBP-1 (p=1.000), IGFBP-2 (p=0.855), IGFBP-3 (p=0.520), IGFBP-4 (p=0.103), IGFBP-5 (p=0.886), or IGFBP-6 (p=0.775). A significant difference was noted between HMB (169.9±23.0ng·ml-1) and PL (207.2±28.0ng·ml-1) for IGFBP-7 at POST (p=0.042). CONCLUSIONS: Although the results of this study do not support the influence of HMB supplementation on circulating concentrations of IGF-1 or IGFBPs1-6 during high intensity military training, it does present initial evidence that it may lower circulating IGFBP-7 concentrations. This may provide some indication of a reduced stress response, but further investigation on the physiological role of IGFBP-7 and military training is needed.

Effects of the phytoestrogen genistein on the porcine anterior pituitary insulin-like growth factor system.

Estrogens have profound effects on the serum and anterior pituitary (AP) insulin-like growth factor (IGF) system in pigs. In this study we determined whether administration of the phytoestrogen genistein increased serum and AP concentrations of IGF-I and relative amounts of serum and AP insulin-like growth factor-binding protein (IGFBP). Twenty barrows of similar age (190 d) and weight (110 kg) were stratified by litter into one of four treatments: controls (C), estradiol (E), 200 mg genistein (G200), and 400 mg genistein (G400). Estradiol-treated pigs were injected daily with 2 mg of estradiol-17ß intramuscularly (i.m.), whereas the G200 and G400 groups were injected daily with either 200 or 400 mg of genistein i.m., respectively, beginning on d 0 and continuing through d 15. Blood was collected on d 0, 3, 6, 9, and 13. Blood and AP were collected at slaughter on d 16. Serum and AP concentrations of IGF-I and luteinizing hormone (LH) were determined by radioimmunoassay. Relative amounts of serum IGFBP were determined by Western ligand blot analysis. Relative expression of AP IGF-I, IGF-I receptor (IGF-IR), gonadotropin-releasing hormone receptor, and LHß subunit was determined by real-time reverse transcriptase polymerase chain reaction. Anterior pituitary concentrations of IGF-I were greater (P > 0.05) in E and G400 pigs compared with controls, whereas AP concentrations of LH were greater (P < 0.05) in G400 pigs compared with C and G200 pigs. Relative expression of LHß was greater in G200 pigs compared with C pigs but did not differ from that in G400 pigs. Relative expression of AP IGF-IR was greater (P < 0.05) in E pigs compared with all other treatments; however, relative expression of AP IGF-IR was greater (P < 0.05) in both G200 and G400 pigs vs C pigs. No differences were detected (P > 0.05) in serum concentrations of IGF-I or relative amounts of serum and AP IGFBP among treatments. These data provide evidence that genistein is capable of modulating components of the AP IGF system that could affect the synthesis and release of LH.

Effects of carbohydrate supplementation on competitive runners undergoing overload training followed by a session of intermittent exercise.

This study evaluated the effects of a micro cycle of overload training (1st-8th day) on metabolic and hormonal responses in male runners with or without carbohydrate supplementation and investigated the cumulative effects of this period on a session of intermittent high-intensity running and maximum-performance-test (9th day). The participants were 24 male runners divided into two groups, receiving 61% of their energy intake as CHO (carbohydrate-group) and 54% in the control-group (CON). The testosterone was higher for the CHO than the CON group after the overload training (694.0 +/- 54.6 vs. CON 610.8 +/- 47.9 pmol/l). On the ninth day participants performed 10 x 800 m at mean 3 km velocity. An all-out 1000 m running was performed before and after the 10 x 800 m. Before, during, and after this protocol, the runners received solution containing CHO or the CON equivalent. The performance on 800 m series did not differ in either group between the first and last series of 800 m, but for the all-out 1000 m test the performance decrement was lower for CHO group (5.3 +/- 1.0 vs. 10.6 +/- 1.3%). The cortisol concentrations were lower in the CHO group in relation to CON group (22.4 +/- 0.9 vs. 27.6 +/- 1.4 pmol/l) and the IGF1/IGFBP3 ratio increased 12.7% in the CHO group. During recovery, blood glucose concentrations remained higher in the CHO group in comparison with the CON group. It was concluded that CHO supplementation possibly attenuated the suppression of the hypothalamic-pituitary-gonadal axis and resulted in less catabolic stress, and thus improved running performance.

Bioactive rather than total IGF-I is involved in acute responses to nutritional interventions in CAPD patients.

BACKGROUND: Inadequate food intake plays an important role in the development of malnutrition in continuous ambulatory peritoneal dialysis (CAPD) patients. Aim of the study. The aim of the study was to investigate in CAPD patients whether circulating insulin-like growth factor-I (IGF-I) bioactivity may offer a more sensitive index to acute nutritional interventions than total IGF-I. METHODS: An open-label, randomized, crossover study of 2 days-with a 1-week interval-was performed in 12 CAPD patients in the fed state to compare a mixture of amino acids (Nutrineal 1.1%) plus glucose (AA plus G) (Physioneal 1.36% to 3.86%) dialysate versus G only as control dialysate. Fed-state conditions were created by identical liquid hourly meals. IGF-I bioactivity was measured by the kinase receptor activation assay (IGF-I KIRA); total IGF-I was measured by immunoassay. RESULTS: In the fed state, both after AA plus G as well as after G dialysis IGF-I bioactivity increased compared to baseline, while no changes in circulating total IGF-I levels were observed in both treatment arms. However, the increase in IGF-I bioactivity was only significant after AA plus G dialysis (P = 0.02). CONCLUSIONS: Our results provide evidence that in CAPD patients changes in circulating IGF-I bioactivity are associated with nutrient intake and that IGF-I bioactivity rather than total IGF-I is involved in acute responses to nutritional interventions in CAPD patients.

Serum insulin-like growth factor-I and insulin-like growth factor binding protein-3 levels in children with zinc deficiency and the effect of zinc supplementation on these parameters.

AIM: To determine the effect of zinc (Zn) therapy on serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) levels in children with Zn deficiency and growth retardation, but without systemic disease, and to investigate the effect of Zn supplementation on these parameters. METHODS: Twenty-nine children (11 girls and 18 boys) were included. Blood samples were obtained for serum IGF-I and IGFBP-3 determination before and after 50 mg/day Zn supplementation for two months. RESULTS: The mean age of the children was 11.0 +/- 3.1 years (range 3.7-16.2 years). Serum IGF-I and IGFBP-3 levels were below the mean values in 28 (96.6%) and all children, respectively. After Zn therapy, serum IGF-I levels were increased in 62% of the children; this increase was statistically significant in 48.3% of the children. Serum IGFBP-3 levels were significantly increased in 10 children. There was a positive correlation between serum Zn level and bone age, and serum IGF-I and IGFBP-3 levels. A positive correlation was present between BMI (r = 0.485, p < 0.001) and serum IGF-I levels before therapy. CONCLUSION: Serum IGF-I and IGFBP-3 levels were decreased in children with Zn deficiency, and were increased after Zn supplementation. In addition, after Zn supplementation, increment of serum IGF-I levels was found to be higher in children with low BMI than those with normal BMI; therefore, the nutritional status of children may also be important, as well as Zn supplementation. Additionally, the determination of higher variation percentile of serum IGF-I level in prepubertal children compared to pubertal children was an interesting finding and necessitates further investigation.

Electroacupuncture promotes insulin-like growth factors system in ovariectomized osteoporosis rats.

Postmenopausal Osteoporosis (PMOP) is induced by the deficiency of estrogen in postmenopausal women. Electroacupuncture (EA) has been confirmed to be effective in clinic. We adopted ovariectomized osteoporosis model of rats to observe the role of EA in PMOP. Fifty female SD rats were divided randomly into 5 groups: intact (INT, n = 10), sham operation (Sham, n = 10), model (n = 10), estrogen (E, n = 10) and electroacupuncture (EA, n = 10). The bone mineral content (BMC) and the bone mineral density (BMD) were examined in lumbar(1-6) and right thigh-bone, respectively, and estrodiol (E(2)), insulin-like growth factor I (IGF-I) and insulin-like growth factor binding proteins (IGF-BPs) were tested by RIA or ELISA. The results showed that BMC and BMD of lumbar 1-6 and right thigh-bone in PMOP model rats decreased markedly, while the level of serum E(2), IGF-I and IGF-BP1 were lower than in INT and Sham. However, EA could upgrade the contents of IGF-I and IGF-BP1 to increase BMD in PMOP rats, while no significant difference was seen in E group. Therefore, EA may promote IGF system to improve PMOP.

Effects of hyperbaric oxygen therapy on circulating interleukin-8, nitric oxide, and insulin-like growth factors in patients with type 2 diabetes mellitus.

BACKGROUND: The potential benefits of hyperbaric oxygen therapy (HBOT) have been reported in diabetic patients with foot ulcers. However, the roles of HBOT on wound healing-associated growth factors and inflammatory mediators are not completely understood in diabetes mellitus (DM). OBJECTIVES: The aim of this study was to investigate the effects of HBOT on circulating cytokines, NO, and insulin-like growth factors (IGF) in patients with type 2 DM. DESIGN AND METHODS: Serum samples were collected from patients with type 2 DM (n=31) and healthy subjects (n=29) before (baseline) and after the first and third exposure. RESULTS: Before HBOT, body mass index (BMI) and serum HbA1c were significantly greater, whereas serum IGF-I was significantly lower in diabetic patients compared to healthy subjects (one-way ANOVA, p<0.05). After adjusting for age, gender, and BMI, serum insulin, growth hormone (GH), IGF-II, IGF-binding protein (IGFBP)-1, IGFBP-3, leptin, interleukin (IL)-8, and NO were not significantly altered by HBOT in diabetic patients and healthy subjects (repeated-measures ANOVA). Change in serum insulin (baseline to the third exposure) was a positive predictor of changes in leptin and NO in healthy subjects and diabetic patients, respectively. CONCLUSIONS: Our results suggest that short-term HBOT may not alter the circulating insulin, IGF, leptin, IL-8, and NO levels. In addition, healthy subjects and diabetic patients showed differential responses to HBOT in the relationships of leptin, insulin, and NO. Further studies are needed to clarify the mechanism of HBOT-improved wound healing in diabetic patients with foot ulcers.

Little effects of insulin-like Growth Factor-I on testicular atrophy induced by hypoxia.

BACKGROUND: Insulin-like Growth Factor-I (IGF-I) supplementation restores testicular atrophy associated with advanced liver cirrhosis that is a condition of IGF-I deficiency. The aim of this work was to evaluate the effect of IGF-I in rats with ischemia-induced testicular atrophy (AT) without liver disease and consequently with normal serum level of IGF-I. METHODS: Testicular atrophy was induced by epinephrine (1, 2 mg/Kg intra-scrotal injection five times per week) during 11 weeks. Then, rats with testicular atrophy (AT) were divided into two groups (n = 10 each): untreated rats (AT) receiving saline sc, and AT+IGF, which were treated with IGF-I (2 microg.100 g b.w.(-1).day(-1), sc.) for 28 d. Healthy controls (CO, n = 10) were studied in parallel. Animals were sacrificed on day 29th. Hypophyso-gonadal axis, IGF-I and IGFBPs levels, testicular morphometry and histopathology, immuno-histochemical studies and antioxidant enzyme activity phospholipid hydroperoxide glutathione peroxidase (PHGPx) were assessed. RESULTS: Compared to controls, AT rats displayed a reduction in testicular size and weight, with histological testicular atrophy, decreased cellular proliferation and transferrin expression, and all of these alterations were slightly improved by IGF-I at low doses. IGF-I therapy increased significantly steroidogenesis and PHGPx activity (p < 0.05). Interestingly, plasma IGF-I did not augment in rats with testicular atrophy treated with IGF-I, while IGFBP3 levels, that reduces IGF-I availability, was increased in this group (p < 0.05). CONCLUSION: In testicular atrophy by hypoxia, condition without IGF-I deficiency, IGF-treatment induces only partial effects. These findings suggest that IGF-I therapy appears as an appropriate treatment in hypogonadism only when this is associated to conditions of IGF-I deficiency (such as Laron Syndrome or liver cirrhosis).

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.

Hematological, metabolic, and endocrine effects of feeding vitamin A and lactoferrin in neonatal calves.

There are reports of important interactions among vitamin A, lactoferrin (Lf), and components of the insulin-like growth factor (IGF) system. Newborn calves are deficient in vitamin A and have a low Lf status. Colostrum contains vitamin A, Lf, and members of the IGF system, including IGF binding proteins (IGFBP), and these compounds may exert mutual interactions in neonatal calves. Effects of feeding different amounts of vitamin A and Lf on hematological, metabolic, and endocrine traits during the first 5 d of life were studied in neonatal calves. Calves were fed a milk-based formula without (F) or with added vitamin A [F(A); 351, 402, 490, and 490 micromol/kg dry matter (DM) on d 1, 2, 3, and 4, respectively], Lf (F(L); 3850, 1990, 660, and 660 mg/kg DM on d 1, 2, 3, and 4, respectively), or vitamin A + Lf (F(AL)) and colostrum (C). Blood samples were taken preprandially on d 1 to 5 and postprandially on d 1, 2, and 4 for the study of hematological, metabolic, and endocrine traits. As intestinal absorption of Lf in formula-fed calves was obviously lower than in colostrum-fed calves, Lf supplementation did not influence the metabolic and endocrine status. Plasma vitamin A concentrations increased from d 1 to 5 in F(A), F(AL), and C, but remained low in F and F(L). Addition of vitamin A to F affected concentrations of vitamin A from d 2 to 5; hemoglobin and triglycerides on d 3; and tended to influence IGFBP-3 levels on d 5. On d 1, preprandial insulin concentrations in F and F(L) were higher than those in F(A) and F(AL) and growth hormone concentrations on d 3 in F(A) were higher than in F(AL). In C, plasma Lf concentrations increased on d 1 and then decreased until d 5, whereas plasma urea and IGF-I concentrations remained stable. Compared with F-fed calves, C-fed calves had higher plasma concentrations of Lf from d 1 to 4, higher concentrations of vitamin A on d 5, higher concentrations of total protein from d 2 to 5, higher concentrations of triglycerides on d 3 and 4, and higher concentrations of IGF-I on d 4 and 5, but lower urea concentrations on d 4 and 5 and lower basal growth hormone concentrations than in F, F(L), and F(A). In conclusion, metabolite and hormone concentrations were influenced by differences in feeding. Addition of vitamin A influenced concentrations of vitamin A, hemoglobin, and triglycerides and tended to affect IGFBP-3 levels. Lactoferrin and vitamin A did not interact with respect to the IGF-I and IGFBP-3 status.

Dietary determinants of circulating insulin-like growth factor (IGF)-I and IGF binding proteins 1, -2 and -3 in women in the Netherlands.

OBJECTIVE: Epidemiological studies suggest that individuals with elevated plasma concentrations of insulin-like growth factor (IGF-I) are at increased risk of developing cancer. We assessed whether dietary intake of total energy, protein, alcohol, phytoestrogens and related foods, and tomatoes and lycopene was associated with plasma levels of IGF-I and IGF binding proteins (IGFBPs) in Dutch women. METHODS: A cross-sectional study was conducted in 224 premenopausal and 162 postmenopausal women, aged 49-69, participating in the Prospect-EPIC study in the Netherlands. Diet was assessed using a food frequency questionnaire. RESULTS: In postmenopausal women, higher alcohol intake was associated with lower plasma IGFBP-1 concentrations (alcohol 1.4 to 20 g/day: 20% decrease in IGFBP-1; p = 0.04), and higher intake of plant lignans was associated with higher IGFBP-1 concentrations (plant lignans 0 to 1 mg/day: 59% increase in IGFBP-1; p =0.02). Higher soy intake was associated with higher plasma IGFBP-2 concentrations in premenopausal women (soy 0 to 2.5 g/day: 3% increase in IGFBP-2; p = 0.04). No independent associations of dietary factors with IGF-I or IGFBP-3 concentrations were observed. However, in premenopausal women alcohol intake was inversely associated with IGF-I and positively associated with IGFBP-3 after mutual adjustment. CONCLUSIONS: In this study population, with limited variation in dietary intake, total energy, protein, phytoestrogens and lycopene were not associated with IGF-I and IGFBP-3. Alcohol was inversely, and some measures of phytoestrogen intake were positively associated with plasma IGFBP-1 or -2 concentrations. The roles of IGFBP-1 and -2 in relation to IGF-I bioactivity and cancer deserve further investigation.

Insulin-like growth factor-I and its binding proteins in colostrum compared to measures in serum of Holstein neonates.

Colostral insulin-like growth factor-I (IGF-I) may be beneficial in the development of gastrointestinal tracts of bovine neonates. Thus, the purpose of this study was to examine relationships among concentrations of IGF-I and IGF-binding proteins (IGFBP) in colostrum used at two initial feedings and serum concentrations of IGF-I, IGFBP, total protein, gamma glutamyltransferase (GGT), and immunoglobulin G at 0 and 48 h after birth in Holstein neonates. Calves (n = 22) were separated from dams immediately after birth. Blood samples were taken before initial feeding and at 48 h after birth. Calves were fed 2 L of colostrum twice and milk replacer thereafter. Linear regression of serum IGF-I at 48 h and colostral IGF-I revealed a significant positive relationship (R2 = 0.204). Serum IGFBP-3 at 48 h and colostral IGFBP-3 also had a positive relationship (R2 = 0.143). However, linear regression of colostral IGF-I on the difference in serum IGF-I at 48 and 0 h was not significant. Calves were assigned to group 1 (0-h serum IGF-I < 10 ng/ml; n = 11) or group 2 (0-h serum IGF-I > or = 10 ng/ml; n = 11) for further analysis. There were no differences in serum IGF-I or IGFBP-2, -3, -4, and -5 concentrations at 48 h between groups 1 and 2. Correlation coefficients revealed negative relationships of serum IGF-I at 0 h to the difference between serum IGF-I at 48 and 0 h (r = -0.824), as well as birth weight of the calf to the amount of GGT at 48 h (r = -0.604). Females had lower birth weights than males, but sex of calf did not affect serum measures. At 0 h, but not 48 h, total serum protein was correlated to serum GGT concentrations (r = 0.573). From indirect evidence, absorption of colostral IGF-I and IGFBP-3 into systemic circulation may occur, but relative importance compared to endogenous sources is uncertain.

Effects of antimicrobials and weaning on porcine serum insulin-like growth factor binding protein levels.

The effects of subtherapeutic antimicrobial supplementation and weaning on serum levels of IGF-I and insulin-like growth factor binding proteins (IGFBP)-2, -3 and -4 were determined in crossbred weanling pigs. At weaning, pigs were allotted to a diet containing 21.8% crude protein and 1.15% lysine with or without Aureozol (110 mg/kg of Aureomycin chlortetracycline, 110 mg/kg of sulfathiazole, and 55 mg/kg of penicillin) for 4 wk. Insulin-like growth factor-binding proteins and IGF-I analyses were performed on blood samples that were drawn weekly. Weaning decreased serum IGFBP-3 levels in both control and Aureozol-treated groups on d 6 and d 14 (P < 0.05) relative to preweaning levels. The IGFBP-3 values returned to preweaning levels by d 21. Although the circulating levels of both the 43-kDa and the 39-kDa glycosylation variants of IGFBP-3 were affected by weaning, the level of the 39-kDa IGFBP-3 was affected relatively more than that of the 43-kDa IGFBP-3 (P < 0.05). Compared with circulating IGFBP-3 levels in control pigs, Aureozol-treated pigs had higher circulating IGFBP-3 levels on d 21 (43%, P < 0.05) and d 27 (46%, P < 0.05). In direct contrast to the effect of weaning on serum IGFBP-3 level, serum IGFBP-2 levels increased on d 6 and d 14 after weaning (P < 0.05) and decreased to preweaning levels by d 21. The IGFBP-2 levels continued to decline and were less than preweaning levels by d 27 (P < 0.05). Aureozol treatment had no effect on serum IGFBP-2 levels at any time. Serum levels of nonglycosylated IGFBP-4 were not affected by either weaning or Aureozol supplementation. Weaning decreased circulating IGF-I concentration on d 6 in both control and Aureozol-treated pigs (76 and 73%, respectively, P < 0.05) and on d 14 (62%, P < 0.05) and d 21 (32%, P < 0.05) in control pigs. Aureozol-supplemented pigs had higher serum IGF-I concentrations than control pigs on d 14 (82%, P < 0.05), d 21 (55%, P < 0.05), and d 27 (36%, P < 0.05). The Aureozol-fed pigs had a 14.2% increase in BW gain (P < 0.05) and a 59.6% increase in ADG (P < 0.05) compared with pigs fed the control diet. Both Aureozol-supplementation and weaning cause changes in serum IGFBP levels and IGF-I concentrations that might be involved in regulating rate and efficiency of growth.

Propionibacteria fed to dairy cows: effects on energy balance, plasma metabolites and hormones, and reproduction.

To determine the effect of feeding Propionibacteria on energy balance, milk yield, and composition, metabolites and hormones of early-lactating dairy cows, multiparous Holstein cows were individually fed a total mixed ration from -2 to 12 wk postpartum with no addition (control, n = 10) or with an additional 17 g of Propionibacteria culture daily (Treated, n = 9). Daily feed intake and milk production were recorded. Plasma cholesterol, nonesterified fatty acids (NEFA), leptin, insulin, glucose, insulin-like growth factor-I (IGF-I), IGF-binding proteins (IGFBP), and progesterone concentrations were measured up to twice weekly. Cows fed supplemental Propionibacteria had improved energy balance at wk 1 of lactation and had lower DMI per kg of body weight than control cows on wk 3 to 7, 10, and 12. Cows fed Propionibacteria had a greater percentage of milk protein and solids-not-fat and plasma NEFA concentrations than did control cows only at wk 1 of lactation. Treatment did not affect milk production or percentage of milk fat and lactose. Leptin levels were greater in treated than control cows throughout the study. Plasma glucose, insulin, cholesterol, IGFBP-3, and IGF-I concentrations were not affected by feeding Propionibacteria, but those variables increased with week postpartum. Plasma IGFBP-2 and IGFBP-5 levels decreased with week postpartum. Measures of reproductive and ovarian function did not differ between Propionibacteria-treated and control cows. Feeding Propionibacteria culture to transition and early lactating dairy cows may hold potential for improved milk protein production and metabolic efficiency during early lactation, without affecting reproductive function.

Effects of a four-day hyperinsulinemic-euglycemic clamp in early and mid-lactation dairy cows on plasma concentrations of metabolites, hormones, and binding proteins.

The effects of insulin, using a 4 d hyperinsulinemic-euglycemic clamp, on plasma concentrations of hormone, metabolites, and binding proteins were evaluated in four Holstein dairy cows during wk 4 and 17 of lactation. Insulin was infused at 1 microg/kg/hr for 96 hr during the clamp period. Compared with the pre-clamp period, plasma insulin concentrations increased 7-fold and 4-fold during the clamp periods in early and mid-lactation, respectively. The total amount of glucose infused was higher (P < 0.05) during the clamp in early lactation. The clamp decreased plasma concentrations of non-esterified fatty acids (P < 0.001) during early lactation while differences in mid-lactation were minor. The clamp also decreased plasma concentration of beta-hydroxybutyrate (P < 0.001), plasma urea nitrogen (P < 0.001), and true protein (P < 0.01) although the patterns of decline differed between early and mid-lactation. Growth hormone (GH) concentrations decreased (P < 0.001) and insulin-like growth factor-1 (IGF-1) increased (P < 0.01) during the clamp period suggesting a direct effect of insulin on the un-coupling of the GH/IGF-1 axis. Levels of IGF binding protein-2 (IGFBP-2) decreased (P < 0.01) during the clamp period. The relative proportion of IGFBP-2 decreased (P < 0.001) and that of IGFBP-3 increased (P < 0.001) during the clamp period. There were no interactions between the clamp period and stage of lactation on GH, IGF-1, or IGFBPs. Overall, most plasma variables measured were affected in the same way during the two clamps, but the pattern of change often varied with stage of lactation.

Effect of type of dialysis membrane on bone in haemodialysis patients.

BACKGROUND: Uraemic bone disease is the result of a number of factors modulating bone formation and resorption in a complex manner. In the present study, the hypothesis tested was that the type of haemodialysis membrane used for renal replacement therapy might also play a role. METHODS: We conducted a prospective, open study in 24 chronic haemodialysis patients who were randomized to dialysis treatment with either cellulosic (CELL group, n=11) or polyacrylonitrile (AN-69 group, n=13) membrane for 9 months. Repeated determinations of plasma parameters reflecting bone turnover were done in all patients, and a bone biopsy in a subgroup at the start and end of study. RESULTS: At the start, mean plasma intact parathyroid hormone levels were comparable between the two groups and they did not vary significantly at 9 months of treatment. Similarly, plasma bone-specific alkaline phosphatase and osteocalcin (markers of bone formation), and cross-laps (marker of bone resorption) remained unchanged. However, plasma insulin-like growth factor-I (IGF-I) progressively decreased from 169 to 119 ng/ml in AN-69 group (P<0.01), whereas it remained unchanged in CELL group. In addition, the levels of IGF binding protein (IGFBP)-1 and IGFBP-2 were increased while the levels of IGFBP-5 were decreased in AN-69 group. In the five patients of each group who had repeat bone biopsies, histomorphometric analysis showed a decrease in osteoblast surface, osteoclast surface and osteoclast number in AN-69 group at 9 months, compared with baseline values measured at the start of the study. In contrast, all three parameters significantly increased in the CELL group at 9 months (P<0.001 for the difference between each of the three parameters). Bone formation rate decreased by 31% in the AN-69 group, but increased by 50% in CELL group. However, this latter difference was not statistically significant. Plasma interleukin (IL)-6 and soluble IL-6 receptor levels did not change in the two groups of patients who had undergone bone biopsy. CONCLUSION: Dialysis with CELL membrane was associated with increased bone turnover whereas the use of AN-69 membrane was associated with decreased bone turnover, suggesting a beneficial effect of the latter on high-turnover uraemic bone disease. However, as the number of patients with repeat bone biopsies was small, these findings need to be confirmed in a larger study. Further studies are also needed to evaluate whether or not the changes in IGF system components play a role in decreased bone cell activity in patients on dialysis using the AN-69 polyacrylonitrile membrane.

Serum insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5 in children with chronic renal failure: relationship to growth and glomerular filtration rate. The European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood. German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

Growth retardation in children with chronic renal failure (CRF) is partly due to an inhibition of insulin-like growth factor (IGF) activity by an excess of high-affinity IGF-binding proteins (IGFBPs). The aim of this study was to analyze the serum levels and forms of IGFBP-4 and IGFBP-5 in CRF patients using specific, recently developed radioimmunoassays (RIAs) and immunoblot analysis. We examined 89 children [age 11.5 (2.8-19.0) years] with CRF [glomerular filtration rate 26.6 (7.0-67.4) ml/min per 1.73 m2], nine of them with end-stage renal disease undergoing peritoneal dialysis. Serum-immunoreactive IGFBP-4 levels were fourfold increased in CRF (prepubertal 1080+/-268 ng/ml; pubertal 989+/-299 ng/ml) compared to healthy prepubertal controls (265+/-73 ng/ml). In contrast, serum IGFBP-5 levels were not significantly increased neither in prepubertal (361+/-120 ng/ml vs 282+/-75 ng/ml in controls) nor pubertal CRF children (478+/-165 ng/ml vs 491+/-80 ng/ml in controls). Immunoblot analysis showed the presence of intact as well as fragmented IGFBP-4 and IGFBP-5. Serum IGFBP-4, but not IGFBP-5, levels were inversely correlated with GFR (r=-0.39, P<0.001). In prepubertal children, IGFBP-4 levels were inversely correlated with standardized height (r=-0.40; P<0.005). In contrast, IGFBP-5 levels were positively correlated both with standardized height (r=0.32, P<0.02) and baseline height velocity (r=0.45, P<0.005). A 3-month therapy with rhGH stimulated serum IGFBP-5 levels by 43% (P<0.01); there was no consistent effect on IGFBP-4 levels. There was a positive correlation between IGFBP-4 and IGFBP-2 (r=0.46, P<0.001); IGFBP-5 was positively correlated with IGF-I (r=0.59, P<0.001), IGF-II(r=0.42, P<0.001)and IGFBP-3 (r=0.47, P<0.001) and inversely correlated with IGFBP-1 (r=-0.41, P<0.001). In summary, serum IGFBP-4 is fourfold elevated in children with CRF in relation to the degree of renal dysfunction and contributes to the marked increase in IGF-binding capacity in CRF serum. The inverse correlation of serum IGFBP-4 with standardized height is consistent with its role as another inhibitor of the biological action of the IGFs on growth plate cartilage. In contrast, serum IGFBP-5 is not elevated in CRF serum and circulates mainly as proteolysed fragments. The positive correlation of serum IGFBP-5 with growth and its increase during GH therapy indicate that IGFBP-5 is a stimulatory IGFBP in patients with CRF, either by enhancing IGF activity through better presentation of TGF to its receptor or by an IGF-independent effect through activation of a specific, recently described putative IGFBP-5-receptor.

IGF-I and IGF-I-binding proteins in rats with adjuvant-induced arthritis given recombinant human growth hormone.

Adjuvant-induced arthritis in rats is associated with growth failure, hypermetabolism and accelerated protein breakdown. We have previously reported that adjuvant-induced arthritis in rats results in a decrease in body weight gain, pituitary GH mRNA, circulating GH and IGF-I together with an increase in serum IGF-binding proteins (IGFBPs). The aim of this study was to analyze the role of GH in the decrease in body weight and in the alterations in the IGF-I system observed in chronic inflammation. Male Wistar rats were injected with complete Freund's adjuvant and 16 days later arthritic rats were injected daily with recombinant human GH (rhGH) (3 IU/kg s.c.) for 8 days; control rats received 250 microl saline. Arthritis significantly decreased body weight gain and serum IGF-I. These decreases were not due to the reduced food intake, since in pair-fed rats they were not observed. Furthermore, administration of rhGH to arthritic rats increased body weight gain without modifying food intake. To further investigate the effect of GH administration, 14 days after adjuvant injection both control and arthritic rats were treated with 0, 1.5, 3 or 6 IU/kg of rhGH. GH treatment at the dose of 3 and 6 IU/kg significantly increased body weight gain in arthritic rats. GH administration, at the higher dose of 6 IU/kg, increased hepatic and serum concentrations of IGF-I in both control and arthritic rats. In control rats, rhGH at the three doses assayed increased circulating IGFBP-3. GH treatment in arthritic rats decreased IGFBP-1 and -2, and did not modify IGFBP-4. GH treatment at the dose of 3 IU/kg also decreased circulating IGFBP-3 in arthritic rats. These data suggest that GH treatment can ameliorate the catabolism observed in adjuvant-induced arthritis, an effect mediated, at least in part, by modifications in the circulating IGFBPs.