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l-Leucine Increases Skeletal Muscle IGF-1 but Does Not Differentially Increase Akt/mTORC1 Signaling and Serum IGF-1 Compared to Ursolic Acid in Response to Resistance Exercise in Resistance-Trained Men.
Church, DD, Schwarz, NA, Spillane, MB, McKinley-Barnard, SK, Andre, TL, Ramirez, AJ, Willoughby, DS
Journal of the American College of Nutrition. 2016;(7):627-638
Abstract
OBJECTIVE Ursolic acid administration following resistance exercise increases mammalian target of rapamycin complex 1 (mTORC1) activity and skeletal muscle IGF-1 concentration in murines in a manner similar to l-leucine yet remains unexamined in humans. This study examined serum and skeletal muscle insulin-like growth factor-1 (IGF-1) and Akt/mTORC1 signaling activity following ingestion of either ursolic acid or l-leucine immediately after resistance exercise. METHODS Nine resistance-trained men performed 3 lower-body resistance exercise sessions involving 4 sets of 8-10 repetitions at 75%-80% one repetition maximum (1-RM) on the angled leg press and knee extension exercises. Immediately following each session, participants orally ingested 3 g cellulose placebo (PLC), l-leucine (LEU), or ursolic acid (UA). Blood samples were obtained pre-exercise and at 0.5, 2, and 6 hours postexercise. Muscle biopsies were obtained pre-exercise and at 2 and 6 hours postexercise. RESULTS Plasma leucine increased in LEU at 2 hours postexercise compared to PLC (p = 0.04). Plasma ursolic acid increased in UA at 2 h and 6 hours postexercise compared to PLC and LEU (p < 0.003). No significant differences were observed for serum insulin (p = 0.98) and IGF-1 (p = 0.99) or skeletal muscle IGF-1 receptor (IGF-1R; p = 0.84), Akt (p = 0.55), mTOR (p = 0.09), and p70S6K (p = 0.98). Skeletal muscle IGF-1 was significantly increased in LEU at 2 hours postexercise (p = 0.03) and 6 hours postexercise (p = 0.04) compared to PLC and UA. CONCLUSION Three grams of l-leucine and ursolic acid had no effect on Akt/mTORC1 signaling or serum insulin or IGF-1; however, l-leucine increased skeletal muscle IGF-1 concentration in resistance-trained men.
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IGF-I at 9 and 36 months of age — relations with body composition and diet at 3 years — the SKOT cohort.
Ejlerskov, KT, Larnkjaer, A, Pedersen, D, Ritz, C, Mølgaard, C, Michaelsen, KF
Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. 2014;(6):239-44
Abstract
OBJECTIVE High infancy levels of insulin-like growth factor-I (IGF-I) have been associated with increased linear growth and fat-free mass (FFM) but also with risk of obesity. This paper examines how IGF-I at 9 and 36 months relates to diet and body composition. DESIGN Healthy term infants from the prospective cohort study, SKOT, were examined at 9 and 36 months with anthropometry, bioelectrical impedance (36 months), 7-day food records and blood analysis of IGF-I and IGFBP-3 by chemiluminescent immunometric assay. RESULTS IGF-I at 36 months (n = 229) was positively correlated with 9 months values and values were considerably higher in girls (43%). Children breastfed at 9 months had lower IGF-I concentrations at 9 months but reached the same IGF-I concentrations at 36 months as infants not breastfed at 9 months. IGF-I at 36 months was positively associated with height, weight, BMI, predicted FFM and FFM index (FFM/height (kg/m2)). Although there also was a positive association with predicted fat mass (FM) there was no association with FM index (FM/height (kg/m2)). Further, a negative association with skin fold thickness was observed. A change in IGF-I from 9–36 months was positively related to FFM and FFM index but not BMI, FM and FM index. No associations were seen between IGF-I and current intake of milk, meat or protein energy percentage, but both fat and saturated fat energy percentage were negatively associated with IGF-I. CONCLUSION IGF-I concentrations were positively associated with growth but not with adiposity at this age. However, the higher tempo of growth may influence age at adiposity rebound and thereby later risk of obesity. Milk and protein intake at 36 months did not influence IGF-I but there was a negative association with intake of fat and saturated fat. The implications of this finding for development of obesity need further exploration.
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Placental calcitriol synthesis and IGF-I levels in normal and preeclamptic pregnancies.
Halhali, A, Díaz, L, Barrera, D, Avila, E, Larrea, F
The Journal of steroid biochemistry and molecular biology. 2014;:44-9
Abstract
Placenta is an extrarenal source of calcitriol and pregnancy is associated with increased maternal serum levels of this hormone. It has been reported that insulin-like growth factor I (IGF-I) stimulates placental calcitriol synthesis and that circulating levels of both hormones are low in preeclampsia. Since calcitriol production has not been determined in placental homogenates in preeclampsia, the aim of the present study was to establish if placental calcitriol synthesis and IGF-I concentration are altered in this tissue obtained from preeclamptic pregnancies. Placental samples were obtained from 8 preeclamptic (PE group) and 8 normotensive (NT group) pregnant women. Calcitriol synthesis was determined using [(3)H]-25(OH)D3 (2.94nM) as precursor and [(3)H]-1,25(OH)2D3 produced was calculated as the percentage of radioactivity co-eluting with unlabelled 1,25(OH)2D3 after two successive high pressure liquid chromatographies. Placental IGF-I levels were determined by RIA. In addition, maternal and umbilical calcitriol and IGF-I levels were also determined in these 2 groups using radioreceptor assay and RIA, respectively. The results of the present study showed that placentas from both groups were able to convert [(3)H]-25(OH)D3 into more polar metabolites. In the PE group, placental [(3)H]-1,25(OH)2D3 synthesis was significantly lower than in the NT group (19.6±6.2 vs 29.9±8.1fmoles/200mg wet weight, P=0.013). Regarding IGF-I, its levels were significantly lower in placentas of the PE group than in the NT group (15.2±3.9 vs 21.6±4.9ng/g wet weight, P=0.012). Maternal and umbilical calcitriol levels were significantly lower in the PE than in the NT group (P<0.001). In the PE group, serum IGF-I levels were significantly lower only in the maternal circulation (P<0.05). In conclusion, placental calcitriol synthesis and IGF-I levels are low in preeclampsia which may contribute to decreased local placental functions related to these two hormones and/or to decreased maternal and fetal pool of 1,25(OH)2D3 during preeclamptic pregnancies. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.
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Insulin-like growth factor I and risk of breast cancer by age and hormone receptor status-A prospective study within the EPIC cohort.
Kaaks, R, Johnson, T, Tikk, K, Sookthai, D, Tjønneland, A, Roswall, N, Overvad, K, Clavel-Chapelon, F, Boutron-Ruault, MC, Dossus, L, et al
International journal of cancer. 2014;(11):2683-90
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Abstract
Experimental evidence shows cross-talk in mammary cells between estrogen, insulin-like growth factor I (IGF-I) and their respective receptors and possible synergistic effects of estrogen receptor (ER) activation and increased IGF-I signaling with regard to breast tumor development, and epidemiological evidence suggests that circulating IGF-I levels may be related more to the risk of ER-positive than ER-negative breast cancer. Using a case-control study nested within the prospective European EPIC cohort (938 breast cancer cases and 1,394 matched control subjects), we analyzed the relationships of prediagnostic serum IGF-I levels with the risk of estrogen and progesterone receptor-positive and -negative breast tumors. IGF-I levels were positively associated with the risk of ER+ breast tumors overall (pre- and postmenopausal women combined, odds ratio (OR)Q4-Q1 = 1.41 [95% confidence interval (CI) 1.01-1.98] for the highest vs. lowest quartile; OR = 1.17 [95% CI 1.04-1.33] per 1-standard deviation (SD) increase in IGF-I, ptrend = 0.01) and among women who were diagnosed with breast cancer at 50 years or older (ORQ3-Q1 = 1.38 [95% CI 1.01-1.89]; OR = 1.19 [95% CI 1.04-1.36] per 1-SD increase in IGF-I, ptrend = 0.01) but not with receptor-positive disease diagnosed at an earlier age. No statistically significant associations were observed for ER- breast tumors overall and by age at diagnosis. Tests for heterogeneity by receptor status of the tumor were not statistically significant, except for women diagnosed with breast cancer at 50 years or older (phet = 0.03 for ER+/PR+ vs. ER-/PR- disease). Our data add to a global body of evidence indicating that higher circulating IGF-I levels may increase risk specifically of receptor-positive, but not receptor-negative, breast cancer diagnosed at 50 years or older.
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Breast-feeding vs formula-feeding for infants born small-for-gestational-age: divergent effects on fat mass and on circulating IGF-I and high-molecular-weight adiponectin in late infancy.
de Zegher, F, Sebastiani, G, Diaz, M, Gómez-Roig, MD, López-Bermejo, A, Ibáñez, L
The Journal of clinical endocrinology and metabolism. 2013;(3):1242-7
Abstract
CONTEXT Fetal growth restraint, if followed by rapid weight gain, confers risk for adult disease including diabetes. How breast-feeding may lower such risk is poorly understood. OBJECTIVE, STUDY PARTICIPANTS, INTERVENTION, OUTCOMES In infants born small-for-gestational-age (SGA), we studied the effects of nutrition in early infancy (breast-feeding vs formula-feeding; BRF vs FOF) on weight partitioning and endocrine markers in late infancy. Body composition (by absorptiometry), fasting glycemia, insulin, IGF-I, and high-molecular-weight (HMW) adiponectin were assessed at 4 and 12 months in BRF controls born appropriate-for-GA (N = 31) and in SGA infants receiving BRF (N = 48) or FOF (N = 51), the latter being randomized to receive a standard formula (FOF1) or a protein-rich formula (FOF2). SETTING The study was conducted in a University Hospital. RESULTS SGA-BRF infants maintained a low fat mass and normal levels of IGF-I and HMW adiponectin. In contrast, SGA-FOF infants normalized their body composition by gaining more fat; this normalization was accompanied by a marked fall in HMW adiponectinemia and, in FOF2 infants, by elevated IGF-I levels. In late infancy, SGA-BRF infants were most sensitive to insulin, even more sensitive than appropriate-for-GA-BRF controls. CONCLUSIONS Because the health perspectives are better for SGA-BRF than for SGA-FOF infants, the present results suggest that FOF for SGA infants should aim at maintaining normal IGF-I and HMW-adiponectin levels rather than at normalizing body composition. Nutriceutical research for SGA infants may thus have to be redirected.
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Effect of insulin therapy on IGF-1 level in children with new-onset type 1 diabetes mellitus: a comparison between DKA and non-DKA.
Shiva, S, Behbod, H, Ghergherechi, R
Journal of pediatric endocrinology & metabolism : JPEM. 2013;(9-10):883-6
Abstract
BACKGROUND AND OBJECTIVE The issue of insulin-like growth factor 1 (IGF-1) and diabetes in adults and type 2 diabetes has been well investigated. A few studies have investigated the serum IGF-1 level at the onset of type 1 diabetes mellitus (T1DM) in children. In the present study, we investigated the IGF-1 level of T1DM children before and after insulin therapy. SUBJECTS AND METHODS Between August 2011 and October 2012, 62 children with newly diagnosed T1DM were recruited. Serum IGF-1 levels were compared before and 1 month after insulin therapy between diabetic ketoacidosis (DKA) and non-DKA patients. RESULTS Thirty-one patients without DKA (18 girls and 13 boys, mean age 8.8 ± 3.01 years) and 31 patients with DKA (18 girls and 13 boys, mean age 8.3 ± 3.7 years) were studied. The mean IGF-1 in the DKA group was lower than that in the non-DKA group; however, this difference was not statistically significant (p=0.10). Serum IGF-1 levels increased significantly 1 month after insulin therapy in both the DKA (p<0.001) and non-DKA (p<0.001) groups. CONCLUSION Serum IGF-1 level is reduced in new-onset T1DM children. A significant increase in serum IGF-1 level can occur with insulin therapy in both DKA and non-DKA children.
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Effects of acute caloric restriction compared to caloric balance on the temporal response of the IGF-I system.
Henning, PC, Scofield, DE, Rarick, KR, Pierce, JR, Staab, JS, Lieberman, HR, Nindl, BC
Metabolism: clinical and experimental. 2013;(2):179-87
Abstract
OBJECTIVE Insulin-like growth factor-I (IGF-I) is a key regulator of metabolism during altered energy states. The IGF-I system components respond to prolonged caloric restriction but it is not clear if this system responds similarly to acute caloric restriction. The purpose of this study was to characterize the IGF-I system response to acute caloric restriction with a secondary purpose of determining if two isocaloric diets with different ratios of carbohydrate to fat alter the IGF-I system under conditions of caloric balance. MATERIALS/METHODS A double-blind, placebo-controlled crossover design was used in which 27 subjects underwent three, 48-h experimental treatments: 1) caloric restriction 2) carbohydrate and 3) carbohydrate/fat. Blood was sampled periodically (6 time points total) for IGF-I (total and free), IGFBPs1-4, insulin and glucose. ANOVAs were used with significance set at P<0.05. RESULTS Total IGF-I decreased 7% during CR (P=0.051) and remained stable during CHO and CHO/F. Free IGF-I decreased 43% during CR (P<0.05) and remained stable during CHO and CHO/F. IGFBP-1 increased by 445% during CR (P<0.05) compared to CHO and CHO/F with no changes for IGFBP-2, IGFBP-3 and IGFBP-4. There was no change in glucose or insulin during CR over the course of the study. Insulin and glucose increased (P<0.05) after a meal in both the CHO and CHO/F groups with no difference between these two groups. CONCLUSION Our findings indicate that free IGF-I decreases and IGFBP-1 increases during caloric restriction, but they are not altered with diets differing in carbohydrate and fat content. Changes in free IGF-I and IGFBP-1 are sensitive to caloric restriction, and their measurement may be valuable in monitoring the physiological response to refeeding in those consuming suboptimal calories.
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Effects of dietary weight loss and exercise on insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in postmenopausal women: a randomized controlled trial.
Mason, C, Xiao, L, Duggan, C, Imayama, I, Foster-Schubert, KE, Kong, A, Campbell, KL, Wang, CY, Alfano, CM, Blackburn, GL, et al
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2013;(8):1457-63
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High levels of insulin-like growth factor (IGF)-I may increase the risk of common cancers in humans. We hypothesized that weight loss induced by diet and/or exercise would reduce IGF-I in postmenopausal women. Four hundred and thirty nine overweight or obese [body mass index (BMI) ≥ 25 kg/m(2)] women (50-75 years) were randomly assigned to: (i) exercise (N = 117), (ii) dietary weight loss (N = 118), (iii) diet + exercise (N = 117), or (iv) control (N = 87). The diet intervention was a group-based program with a 10% weight loss goal. The exercise intervention was 45 minutes/day, 5 days/week of moderate-to-vigorous intensity activity. Fasting serum IGF-I and IGF-binding protein (IGFBP)-3 were measured at baseline and 12 months by radioimmunoassay. Higher baseline BMI was associated with lower IGF-I and IGF-I/IGFBP-3 molar ratio. Although no significant changes in either IGF-I or IGFBP-3 were detected in any intervention arm compared with control, the IGF-I/IGFBP-3 ratio increased significantly in the diet (+5.0%, P < 0.01) and diet + exercise (+5.4%, P < 0.01) groups compared with control. Greater weight loss was positively associated with change in both IGF-I (P(trend) = 0.017) and IGF-I/IGFBP-3 ratio (P(trend) < 0.001) in the diet group, but inversely with change in IGFBP-3 in the diet + exercise group (P(trend) = 0.01). No consistent interaction effects with baseline BMI were detected. Modified IGF-I bioavailability is unlikely to be a mechanism through which caloric restriction reduces cancer risk in postmenopausal women.
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Effects of aggressive parenteral nutrition on growth and clinical outcome in preterm infants.
Can, E, Bülbül, A, Uslu, S, Cömert, S, Bolat, F, Nuhoğlu, A
Pediatrics international : official journal of the Japan Pediatric Society. 2012;(6):869-74
Abstract
BACKGROUND The goal of nutrition in the preterm infant is to achieve postnatal growth approximating normal fetal growth. During the early postnatal period, protein intake must be sufficient to achieve normal postnatal growth in extremely low-birthweight infants. The aim of this study was to test the hypothesis that giving higher amounts of amino acids and lipids to infants born at <34 gestational weeks (GW) may improve growth at the 40th week of gestation and have a positive preventive effect on development of retinopathy of prematurity (ROP). METHODS Fifty-three neonates born at <34 GW and hospitalized in the neonatal intensive care unit (NICU) were included in this prospective study. They were randomly divided into two groups. Group 1 received aggressive parenteral nutrition (PN) (amino acids 3 g/kg per day and lipids 2 g/kg per day on first day of life). Group 2 received conventional PN (amino acids 1.5 g/kg per day and lipids 1 g/kg per day on first day of life). The anthropometric measurements, clinical outcomes and serum levels of insulin-like growth factor-I (IGF-I), IGF binding protein (IGFBP) and thyroid hormones were compared between groups. RESULTS At 40 weeks of gestation, height, head circumference and serum IGF-I and IGFBP3 were statistically higher in the group receiving aggressive PN. Thyroid hormones were not affected by aggressive PN. The lower levels of IGF-I and IGFBP3 in the group receiving conventional PN were negatively correlated with development of ROP. CONCLUSION Aggressive PN seems to positively affect neonates' anthropometric measurements at the 40th gestational week and the development of ROP. These effects may be related to high levels of IGF-I and IGFBP3.
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Serum IGF-1 concentrations change with soy and seaweed supplements in healthy postmenopausal American women.
Teas, J, Irhimeh, MR, Druker, S, Hurley, TG, Hébert, JR, Savarese, TM, Kurzer, MS
Nutrition and cancer. 2011;(5):743-8
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Insulin-like growth factor 1 (IGF-1) is an anabolic hormone important for growth and development. However, high-circulating serum concentrations in adults are associated with increased risk of postmenopausal breast cancer. Nutritional status and specific foods influence serum IGF-1 concentrations. Breast cancer incidence is typically low in Asian countries where soy is commonly consumed. Paradoxically, soy supplement trials in American women have reported significant increases in IGF-1. Seaweed also is consumed regularly in Asian countries where breast cancer risk is low. We investigated the possibility that seaweed could modify soy-associated increases in IGF-1 in American women. Thirty healthy postmenopausal women (mean age 58 yr) participated in this 14-wk double-blinded, randomized, placebo-controlled crossover clinical trial. Participants consumed 5 g/day placebo or seaweed (Alaria esculenta) in capsules for 7 wk. During the 7th wk, a high-soy protein isolate powder was added (2 mg/kg body weight aglycone equivalent isoflavones). Overnight fasting blood samples were collected after each intervention period. Soy significantly increased serum IGF-1 concentrations compared to the placebo (21.2 nmol/L for soy vs. 16.9 nmol/L for placebo; P = 0.0001). The combination of seaweed and soy significantly reduced this increase by about 40% (21.2 nmol/L for soy alone vs. 19.4 nmol/L; P = 0.01). Concurrent seaweed and soy consumption may be important in modifying the effect of soy on IGF-1 serum concentrations.