| 1. |
- Rajewsky, N., et al.
(författare)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Tidskriftsartikel (refereegranskat)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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| 2. |
- van Es, Michael A, et al.
(författare)
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Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis
- 2009
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:10, s. 1083-1087
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a genome-wide association study among 2,323 individuals with sporadic amyotrophic lateral sclerosis (ALS) and 9,013 control subjects and evaluated all SNPs with P < 1.0 x 10(-4) in a second, independent cohort of 2,532 affected individuals and 5,940 controls. Analysis of the genome-wide data revealed genome-wide significance for one SNP, rs12608932, with P = 1.30 x 10(-9). This SNP showed robust replication in the second cohort (P = 1.86 x 10(-6)), and a combined analysis over the two stages yielded P = 2.53 x 10(-14). The rs12608932 SNP is located at 19p13.3 and maps to a haplotype block within the boundaries of UNC13A, which regulates the release of neurotransmitters such as glutamate at neuromuscular synapses. Follow-up of additional SNPs showed genome-wide significance for two further SNPs (rs2814707, with P = 7.45 x 10(-9), and rs3849942, with P = 1.01 x 10(-8)) in the combined analysis of both stages. These SNPs are located at chromosome 9p21.2, in a linkage region for familial ALS with frontotemporal dementia found previously in several large pedigrees.
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| 3. |
- van Es, Michael A, et al.
(författare)
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Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis
- 2011
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Ingår i: Annals of Neurology. - : Wiley-Blackwell. - 0364-5134 .- 1531-8249. ; 70:6, s. 964-973
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD.METHODS: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios.RESULTS: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10(-6) for ALS and p = 4.3 × 10(-5) for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD.INTERPRETATION: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD.
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| 4. |
- van Es, Michael A, et al.
(författare)
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Genetic variation in DPP6 is associated with susceptibility to amyotrophic lateral sclerosis.
- 2008
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:1, s. 29-31
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Tidskriftsartikel (refereegranskat)abstract
- We identified a SNP in the DPP6 gene that is consistently strongly associated with susceptibility to amyotrophic lateral sclerosis (ALS) in different populations of European ancestry, with an overall P value of 5.04 x 10(-8) in 1,767 cases and 1,916 healthy controls and with an odds ratio of 1.30 (95% confidence interval (CI) of 1.18-1.43). Our finding is the first report of a genome-wide significant association with sporadic ALS and may be a target for future functional studies.
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| 5. |
- Blauw, Hylke M, et al.
(författare)
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A large genome scan for rare CNVs in amyotrophic lateral sclerosis
- 2010
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Ingår i: Human Molecular Genetics. - : Oxford Journals. - 0964-6906 .- 1460-2083. ; 19:20, s. 4091-4099
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease selectively affecting motor neurons in the brain and spinal cord. Recent genome-wide association studies (GWASs) have identified several common variants which increase disease susceptibility. In contrast, rare copy-number variants (CNVs), which have been associated with several neuropsychiatric traits, have not been studied for ALS in well-powered study populations. To examine the role of rare CNVs in ALS susceptibility, we conducted a CNV association study including over 19,000 individuals. In a genome-wide screen of 1875 cases and 8731 controls, we did not find evidence for a difference in global CNV burden between cases and controls. In our association analyses, we identified two loci that met our criteria for follow-up: the DPP6 locus (OR = 3.59, P = 6.6 × 10(-3)), which has already been implicated in ALS pathogenesis, and the 15q11.2 locus, containing NIPA1 (OR = 12.46, P = 9.3 × 10(-5)), the gene causing hereditary spastic paraparesis type 6 (HSP 6). We tested these loci in a replication cohort of 2559 cases and 5887 controls. Again, results were suggestive of association, but did not meet our criteria for independent replication: DPP6 locus: OR = 1.92, P = 0.097, pooled results: OR = 2.64, P = 1.4 × 10(-3); NIPA1: OR = 3.23, P = 0.041, pooled results: OR = 6.20, P = 2.2 × 10(-5)). Our results highlight DPP6 and NIPA1 as candidates for more in-depth studies. Unlike other complex neurological and psychiatric traits, rare CNVs with high effect size do not play a major role in ALS pathogenesis.
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| 6. |
- Van Es, Michael A, et al.
(författare)
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Analysis of FGGY as a risk factor for sporadic amyotrophic lateral sclerosis
- 2009
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Ingår i: Amyotrophic Lateral Sclerosis and other Motor Neuron Disorders. - : Informa UK Limited. - 1466-0822 .- 1743-4483. ; 10:5-6, s. 441-447
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Tidskriftsartikel (refereegranskat)abstract
- A genome-wide association study (GWAS) using pooled DNA samples from 386 sporadic ALS patients and 542 controls from the USA, identified genetic variation in FGGY (FLJ10986) as a risk factor, as well as 66 additional candidate SNPs. Considering the large number of hypotheses that are tested in GWAS, independent replication of associations is crucial for identifying true-positive genetic risk factors for disease. The primary aim of this study was to study the association between FGGY and sporadic ALS in large, homogeneous populations from northern Europe. Genotyping experiments were performed using Illumina Beadchips, Sequenom iPLEX assays and Taqman technology on large case-control series from The Netherlands, Belgium, Sweden and Ireland (total: 1883 sporadic ALS patients and 2063 controls). No significant association between sporadic ALS and the six previously reported associated SNPs in FGGY was observed: rs6700125 (p =0.56), rs6690993 (p =0.30), rs10493256 (p =0.68), rs6587852 (p =0.64), rs1470407 (p =0.28) and rs333662 (p =0.44). Screening of the additional candidate loci did not yield significant associations either, with the lowest p-value in joint analysis for rs7772593 (p =0.14). We concluded that common genetic variation in FGGY is not associated with susceptibility to sporadic ALS in genetically homogeneous populations from northern Europe.
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| 7. |
- van Es, Michael A, et al.
(författare)
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ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis : a genome-wide association study.
- 2007
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Ingår i: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 6:10, s. 869-77
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating disease characterised by progressive degeneration of motor neurons in the brain and spinal cord. ALS is thought to be multifactorial, with both environmental and genetic causes. Our aim was to identify genetic variants that predispose for sporadic ALS. METHODS: We did a three-stage genome-wide association study in 461 patients with ALS and 450 controls from The Netherlands, using Illumina 300K single-nucleotide polymorphism (SNP) chips. The SNPs that were most strongly associated with ALS were analysed in a further 876 patients and 906 controls in independent sample series from The Netherlands, Belgium, and Sweden. We also investigated the possible pathological functions of associated genes using expression data from whole blood of patients with sporadic ALS and of control individuals who were included in the genome-wide association study. FINDINGS: A genetic variant in the inositol 1,4,5-triphosphate receptor 2 gene (ITPR2) was associated with ALS (p=0.012 after Bonferroni correction). Combined analysis of all samples (1337 patients and 1356 controls) confirmed this association (p=3.28x10(-6), odds ratio 1.58, 95% CI 1.30-1.91). ITPR2 expression was greater in the peripheral blood of 126 ALS patients than in that of 126 healthy controls (p=0.00016). INTERPRETATION: Genetic variation in ITPR2 is a susceptibility factor for ALS. ITPR2 is a strong candidate susceptibility gene for ALS because it is involved in glutamate-mediated neurotransmission, is one of the main regulators of intracellular calcium concentrations, and has an important role in apoptosis.
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| 8. |
- van Rheenen, Wouter, et al.
(författare)
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H63D polymorphism in HFE is not associated with amyotrophic lateral sclerosis
- 2013
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 34:5, s. 1517.e5-1517.e7
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Tidskriftsartikel (refereegranskat)abstract
- The H63D polymorphism in HFE has frequently been associated with susceptibility to amyotrophic lateral sclerosis (ALS). Regarding the role of HFE in iron homeostasis, iron accumulation is considered an important process in ALS. Furthermore, novel therapeutic strategies are being developed targeting this process. Evidence for this genetic association is, however, limited to several small studies. For this reason we studied the H63D polymorphism in a large European cohort including 3962 ALS patients and 5072 control subjects from 7 countries. After meta-analysis of previous studies and current findings we conclude that the H63D polymorphism in HFE is not associated with susceptibility to ALS, age at disease onset, or survival. (C) 2013 Elsevier Inc. All rights reserved.
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| 9. |
- Diekstra, Frank P., et al.
(författare)
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Mapping of Gene Expression Reveals CYP27A1 as a Susceptibility Gene for Sporadic ALS
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:4, s. e35333-
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disease characterized by loss of upper and lower motor neurons. ALS is considered to be a complex trait and genome-wide association studies (GWAS) have implicated a few susceptibility loci. However, many more causal loci remain to be discovered. Since it has been shown that genetic variants associated with complex traits are more likely to be eQTLs than frequency-matched variants from GWAS platforms, we conducted a two-stage genome-wide screening for eQTLs associated with ALS. In addition, we applied an eQTL analysis to finemap association loci. Expression profiles using peripheral blood of 323 sporadic ALS patients and 413 controls were mapped to genome-wide genotyping data. Subsequently, data from a two-stage GWAS (3,568 patients and 10,163 controls) were used to prioritize eQTLs identified in the first stage (162 ALS, 207 controls). These prioritized eQTLs were carried forward to the second sample with both gene-expression and genotyping data (161 ALS, 206 controls). Replicated eQTL SNPs were then tested for association in the second-stage GWAS data to find SNPs associated with disease, that survived correction for multiple testing. We thus identified twelve cis eQTLs with nominally significant associations in the second-stage GWAS data. Eight SNP-transcript pairs of highest significance (lowest p = 1.27 x 10(-51)) withstood multiple-testing correction in the second stage and modulated CYP27A1 gene expression. Additionally, we show that C9orf72 appears to be the only gene in the 9p21.2 locus that is regulated in cis, showing the potential of this approach in identifying causative genes in association loci in ALS. This study has identified candidate genes for sporadic ALS, most notably CYP27A1. Mutations in CYP27A1 are causal to cerebrotendinous xanthomatosis which can present as a clinical mimic of ALS with progressive upper motor neuron loss, making it a plausible susceptibility gene for ALS.
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| 10. |
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| 11. |
- Diekstra, Frank P., et al.
(författare)
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UNC13A is a modifier of survival in amyotrophic lateral sclerosis
- 2012
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 33:3, s. 630.e3-630.e8
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Tidskriftsartikel (refereegranskat)abstract
- A large genome-wide screen in patients with sporadic amyotrophic lateral sclerosis (ALS) showed that the common variant rs12608932 in gene UNC13A was associated with disease susceptibility. UNC13A regulates the release of neurotransmitters, including glutamate. Genetic risk factors that, in addition, modify survival, provide promising therapeutic targets in ALS, a disease whose etiology remains largely elusive. We examined whether UNC13A was associated with survival of ALS patients in a cohort of 450 sporadic ALS patients and 524 unaffected controls from a population-based study of ALS in The Netherlands. Additionally, survival data were collected from individuals of Dutch, Belgian, or Swedish descent (1767 cases, 1817 controls) who had participated in a previously published genome-wide association study of ALS. We related survival to rs12608932 genotype. In both cohorts, the minor allele of rs12608932 in UNC13A was not only associated with susceptibility but also with shorter survival of ALS patients. Our results further corroborate the role of UNC13A in ALS pathogenesis. (C) 2012 Elsevier Inc. All rights reserved.
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| 12. |
- van Vught, A. J. A. H., et al.
(författare)
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The effects of dietary protein on the somatotropic axis : a comparison of soy, gelatin, alpha-lactalbumin and milk
- 2010
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 64:5, s. 441-446
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/OBJECTIVES: Growth hormone (GH) is an important regulator of growth and body composition. It has been shown that GH release can be promoted by administration of various amino acids (AAs), such as arginine and lysine, that are present in soy protein. We previously showed that oral ingestion of soy protein stimulates the GH release, it is not known however to which extent other proteins stimulate the GH secretion.SUBJECTS/METHODS: Ingestion of soy protein (soy), gelatin protein (gelatin), alpha-lactalbumin protein (alpha-lactalbumin) and milk protein (milk) were compared on their GH-stimulating capacity. After oral ingestion of protein (0.6 g protein per kg bodyweight), blood was sampled every 20 min for 5 h to analyze GH, AA, insulin and glucose concentrations. The study was performed in eight healthy women (aged 19-26 years; body mass index 19-26 kg/m(2)) in a randomized, single blind, placebo-controlled crossover design.RESULTS: GH responses were more increased after ingestion of gelatine (8.2+/-1.1 microg/l) compared with ingestion of soy, alpha-lactalbumin and milk (5.0+/-0.8, 4.5+/-0.6 and 6.4+/-1.0 microg/l, respectively) (P<0.05). After ingestion of each protein, GH responses were higher compared with placebo ingestion (P<0.05). Simultaneously ingestion of gelatin resulted in the highest serum-arginine concentrations (ARG) compared with after ingestion of the other proteins (P<0.05). Insulin as well as glucose concentrations were not different after ingestion of the various proteins (P<0.05).CONCLUSIONS: The GH-promoting activity of protein depends on the protein source, in that, gelatin protein is the most potent GH stimulator. Arginine may be the responsible AA in the GH-promoting effect of gelatin, although each protein may have its own specific AA-spectrum involved in the stimulation of the somatotropic axis.
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| 13. |
- van Vught, A. J. A. H., et al.
(författare)
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The effects of protein ingestion on GH concentrations in visceral obesity
- 2010
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Ingår i: Hormone and Metabolic Research. - : Georg Thieme Verlag KG. - 0018-5043 .- 1439-4286. ; 42:10, s. 740-745
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Tidskriftsartikel (refereegranskat)abstract
- Growth hormone (GH), a hormone originating from the anterior pituitary gland, is an important regulator of metabolism and body composition. Low GH secretion is associated with features of the metabolic syndrome, in particular increased visceral body fat and decreased lean body mass. It has been shown that GH release can be promoted by ingestion of protein, in particular gelatin protein. The question remains; is the GH-promoting effect of gelatin protein also present in a population with blunted GH response, such as visceral obesity? 8 lean women (age: 23 +/- 3 years, BMI: 21.6 +/- 2.0 kg/m(2)) and 8 visceral obese women (age: 28 +/- 7 years, BMI: 33.8 +/- 5.5 kg/m(2)) were compared with regard to their 5-h GH response after oral ingestion of gelatin protein (0.6 g protein per kg bodyweight), placebo (water), or injection of growth hormone releasing hormone (GHRH) (1 mu/kg body weight), in a randomized crossover design. GH response after placebo, gelatin protein, or GHRH was higher in lean subjects than in visceral obese subjects (p < 0.05). Ingestion of gelatin protein increased GH response compared with placebo in both visceral obese (182.1 +/- 81.6 mu g/l.5h vs. 28.4 +/- 29.8 mu g/l.5h) and lean (631.7 +/- 144.2 mu g/l.5h vs. 241.0 +/- 196.8 mu g/l.5h) subjects (p < 0.05). GH response after ingestion of gelatin protein in visceral obese did not differ from that in lean, placebo-treated subjects (p = 0.45). GH concentrations after GHRH injection correlated significantly with GH concentrations after gelatin ingestion (AUC; r = 0.71, p < 0.01, Peak; r = 0.81, p < 0.01). Further research is needed to investigate if gelatin protein is able to improve metabolic abnormalities in hyposomatotropism in the long term or to investigate the relevance of protein as diagnostic tool in hyposomatotropism.
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| 14. |
- Veldhorst, Margriet A. B., et al.
(författare)
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Dose-dependent satiating effect of whey relative to casein or soy
- 2009
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Ingår i: Physiology and Behavior. - Amsterdam : Elsevier. - 0031-9384 .- 1873-507X. ; 96:4-5, s. 675-682
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Tidskriftsartikel (refereegranskat)abstract
- Dietary protein plays a role in body weight regulation, partly because of its effects on appetite. The objective was to compare the effects of high or normal casein-, soy-, or whey-protein breakfasts on appetite, specific hormones, amino acid responses and subsequent energy intake. Twenty-five healthy subjects (mean+/-SEMBMI:23.9+/-0.3 kg/m2; age:22+/-1 years) received standardized breakfasts: custards with either casein-, soy, or whey-protein with either 10/55/35 (normal) or 25/55/20 (high)En% protein/carbohydrate/fat in a randomized, single-blind design. Appetite profile (Visual Analogue Scales) and amino acid concentrations were determined for 4 h whereas plasma glucose, insulin, active Glucagon-like Peptide 1 (GLP-1), and active ghrelin concentrations were determined for 3 h; the sensitive moment for lunch was determined. Subjects returned for a second set of experiments and received the same breakfasts, ad lib lunch was offered 180 min later; energy intake (EI) was assessed. At 10En%, whey decreased hunger more than casein or soy (p <0.05), coinciding with higher leucine, lysine, tryptophan, isoleucine, and threonine responses (p<0.05). At 25En% there were no differences in appetite ratings. Whey triggered the strongest responses in concentrations of active GLP-1 (p<0.05) and insulin (p<0.05) compared with casein and/or soy. There were no differences in EI. In conclusion, differences in appetite ratings between different proteins appeared at a normal concentration; at 10En% whey-protein decreased hunger more than casein- or soy-protein. At 25En% whey-protein triggered stronger responses in hormone concentrations than casein- or soy-protein. The results suggest that a difference in appetite ratings between types of protein appears when certain amino acids are above and below particular threshold values.
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| 15. |
- van Vught, Anneke J. A. H., et al.
(författare)
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Association between dietary protein and change in body composition among children (EYHS)
- 2009
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Ingår i: Clinical Nutrition. - : Churchill Livingstone. - 0261-5614 .- 1532-1983. ; 28:6, s. 684-688
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Growth hormone (GH) affects body composition by a relatively reduced fat mass and increased fat free mass. The intake of protein as well as the specific amino acids arginine and lysine potently stimulate GH secretion. This study investigated associations between intakes of protein, arginine, lysine and subsequent 6-year change in body composition among 8-10-year-old children.METHODS: Data of 364 children were collected from Odense, Denmark, during 1997-1998 and 6-year later as part of the European Youth Heart Study. Body mass index among children was subdivided by fat free mass index (FFMI) and fat mass index (FMI), based on skinfold measurements. Dietary intake was estimated via 24h recall. Associations between intakes of protein as well as arginine, lysine and change in FFMI and FMI were analysed by multiple linear regressions, adjusted for social economic status, puberty stage and physical activity level.RESULTS: Among lean girls inverse associations were found between protein as well as arginine and lysine intake and change in fat mass index (beta=-1.12+/-0.56, p=0.03, beta=-1.10+/-0.53, p=0.04, beta=-1.13+/-0.51, p=0.03 respectively). Furthermore among girls with a body mass index in the 5th quintile, protein intake was associated with DeltaFFMI (p=0.04), and more specific when LYS intake was high, ARG intake was associated with DeltaFFMI (p=0.04).CONCLUSION: Among girls high protein intakes may decrease body fat gain and increase fat free mass gain, depending on the available amounts and combinations of arginine and lysine.
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| 16. |
- van Vught, Anneke J. A. H., et al.
(författare)
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Association between intake of dietary protein and 3-year-change in body growth among normal and overweight 6-year-old boys and girls (CoSCIS)
- 2010
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Ingår i: Public Health Nutrition. - Cambridge United Kingdom : Cambridge University Press. - 1368-9800 .- 1475-2727. ; 13:5, s. 647-653
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Growth hormone (GH) affects linear growth and body composition, by increasing the secretion of insulin-like growth factor-I (IGF-I), muscle protein synthesis and lipolysis. The intake of protein (PROT) as well as the specific amino acids arginine (ARG) and lysine (LYS) stimulates GH/IGF-I secretion. The present paper aimed to investigate associations between PROT intake as well as intake of the specific amino acids ARG and LYS, and subsequent 3-year-change in linear growth and body composition among 6-year-old children.Design: Children's data were collected from Copenhagen (Denmark), during 2001-2002, and again 3 years later. Boys and girls were separated into normal weight and overweight, based on BMI quintiles. Fat-free mass index (FFMI) and fat mass index (FMI) were calculated. Associations between change (Delta) in height, FMI and FFMI, respectively, and habitual PROT intake as well as ARG and LYS were analysed by multiple linear regressions, adjusted for baseline height, FMI or FFMI and energy intake, age, physical activity and socio-economic status.Setting: Eighteen schools in two suburban communities in the Copenhagen (Denmark) area participated in the study. SUBJECTS: In all, 223 children's data were collected for the present study.Results: High ARG intake was associated with linear growth (beta = 1.09 (se 0.54), P = 0.05) among girls. Furthermore, in girls, DeltaFMI had a stronger inverse association with high ARG intake, if it was combined with high LYS intake, instead of low LYS intake (P = 0.03). No associations were found in boys.Conclusion: In prepubertal girls, linear growth may be influenced by habitual ARG intake and body fat gain may be relatively prevented over time by the intake of the amino acids ARG and LYS.
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| 17. |
- van Vught, Anneke J. A. H., et al.
(författare)
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Pharmacological and physiological growth hormone stimulation tests to predict successful GH therapy in children
- 2009
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Ingår i: Journal of Pediatric Endocrinology & Metabolism (JPEM). - : Walter de Gruyter. - 0334-018X .- 2191-0251. ; 22:8, s. 679-694
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Forskningsöversikt (refereegranskat)abstract
- Although the current use of growth hormone (GH) stimulation tests (GHSTs) is still subject to debate, the tests are widely used to diagnose GH deficiency. This literature review evaluates primarily the sensitivity, specificity and reliability of GHSTs and secondarily their convenience. Single pharmacological tests typically address only a single pathway in the complex physiological regulation of GH secretion and are therefore characterized by lower sensitivity, specificity and reliability than combined pharmacological tests or physiological tests. In spite of the high levels of sensitivity, specificity and reliability, physiological tests require considerably more effort to perform, from the physician as well as from the child. Therefore, a need for an alternative, convenient, physiological GHST still remains. Oral ingestion of dietary protein is convenient in practice and may induce more physiological stimulation of GH secretion, hence may be a promising valuable addition to the existing GHSTs in GH deficiency.
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| 18. |
- van Vught, Anneke J. A. H., et al.
(författare)
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Effects of oral ingestion of amino acids and proteins on the somatotropic axis
- 2008
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - Chevy Chase, Md. : Endocrine society. - 0021-972X .- 1945-7197. ; 93:2, s. 584-590
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: GH is an important regulator of growth and body composition. It has been shown that GH release can be promoted by iv as well as oral administration of various amino acids (AAs), especially arginine (ARG) and lysine (LYS), which are amply present in soy protein. However, the effects of dietary protein on GH secretion are less well described. OBJECTIVE AND DESIGN: In an experiment, we compared the effects of oral ingestion of a mixture reflecting the AA composition of soy protein (AA), with oral ingestion of ARG + LYS, on GH secretion in eight healthy women (body mass index 19-25 kg/m(2); age, 18-24 yr). In a second experiment, we compared oral ingestion of hydrolyzed soy protein and complete soy protein with the AA mixture on GH secretion in eight healthy women (body mass index 19-26 kg/m(2); age, 19-36 yr). Both experiments were performed in a randomized, single-blind crossover design. GH, insulin, glucose, and plasma AA were determined every 20 min, during 3 h in the first experiment and during 5 h in the second experiment. RESULTS: Peak values of GH were higher after ingestion of the AA mixture compared with ingestion of ARG + LYS (P < 0.05). GH responses, as determined by area under the curve, did not significantly differ after ingestion of the complete soy protein, hydrolyzed soy protein, or AA mixture but were all higher than after placebo (P < 0.05). Insulin responses (area under the curve) were higher after ingestion of hydrolyzed soy protein, complete soy protein, and AA mixture, compared with placebo (P < 0.05). Glucose concentrations were unaffected. CONCLUSION: Ingestion of soy protein, either hydrolyzed or intact, as well as AAs reflecting soy protein, stimulates GH release to a similar extent.
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| 19. |
- van Vught, Anneke J. A. H., et al.
(författare)
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Somatotropic responses to soy protein alone and as part of a meal
- 2008
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Ingår i: European Journal of Endocrinology. - Oslo : Scandinavian Univ. Press. - 0804-4643 .- 1479-683X. ; 159:1, s. 15-18
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: GH is an important regulator of growth and body composition. We previously showed that GH release can be promoted by oral ingestion of soy protein; it is not known, however, whether these somatotropic effects of soy protein are also present when soy protein is ingested as part of a complete meal. OBJECTIVE/DESIGN: We compared the effects of oral ingestion of soy protein alone with the effects of a meal containing the same amount of soy protein on GH secretion in six healthy women (body mass index 19-26 kg/m(2), 19-36 years), in a randomized crossover design. During the whole experiment, serum GH, insulin, and glucose were determined every 20 min. RESULTS: GH responses as determined by area under the curve (AUC) and peak values were lower after ingestion of the meal, in comparison with GH responses after the soy protein consumption alone (P<0.05), and did not differ from the placebo. Glucose and insulin responses, both determined as AUC and peak values, were higher after ingestion of the meal, compared with those after ingestion of the protein drink or the placebo (P<0.05). CONCLUSION: The somatotropic effect of soy protein is reduced and delayed when soy protein is ingested as part of a complete meal. Dietary carbohydrates, by increasing serum levels of glucose and insulin concentration, as well as dietary fat, may have interfered with the somatotropic effects of soy protein.
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