272 research outputs found
Adiponectin isoforms, insulin resistance and liver histology in nonalcoholic fatty liver disease
No full textBackground: Nonalcoholic fatty liver disease is associated with insulin resistance and low adiponectin levels. Adiponectin circulates as high-, medium- and low-molecular weight complexes, possibly exerting different insulin-sensitising effects.
Aim: We investigated adiponectin isoforms in nonalcoholic fatty liver disease in relation to liver disease severity and insulin resistance.
Patients and methods: Total adiponectin and isoform distribution were measured in 54 biopsy-proven, non-diabetic nonalcoholic fatty liver disease subjects, divided according to their fasting and 120-min glucose levels during an oral glucose tolerance test, as well as in 44 matched healthy controls. Insulin resistance/sensitivity was estimated in nonalcoholic fatty liver disease by the homeostasis model assessment and the oral glucose insulin sensitivity during oral glucose tolerance test. Total adiponectin and adiponectin isoforms were determined by in-house assays.
Results: Total adiponectin was reduced in nonalcoholic fatty liver disease (5.32±1.85 mg/L vs. 9.11±3.46 mg/L), with a relative abundance of high-molecular weight (34% vs. 47%) and low-molecular weight adiponectin (16% vs. 19%), coupled with dearth of medium-molecular weight adiponectin (50% vs. 34%) (P < 0.001 for all comparisons). In nonalcoholic fatty liver disease, adiponectin did not differ in relation to homeostasis model assessment, but levels were remarkably higher in relation to oral glucose insulin sensitivity-determined insulin sensitivity. However, the distribution of isoforms did not vary with disease severity, BMI class, glucose regulation or insulin resistance.
Conclusion: Adiponectin levels are reduced in nonalcoholic fatty liver disease, without any significant contribution of isoform distribution to progressive liver disease
Free insulin-like growth factors – measurements and relationships to growth hormone secretion and glucose homeostasis
No full text
Moderate energy restriction-induced weight loss affects circulating IGF levels independent of dietary composition
No full textLink to a related website: https://eje.bioscientifica.com/downloadpdf/journals/eje/162/6/1075.pdf, Open Access via UnpaywallBackground: Obesity is associated with major changes in the circulating IGF system. However, it is not clear to what extent the IGF system is normalized following diet, and the possible role of different types of diet is also unknown.
Conclusions: Weight loss induced by moderate energy restriction modulated the IGF system independent of dietary protein or red meat content. The effect of diet on IGFBP-2 appeared to have limited biological effect as total IGF2 and pro-IGF2 did not change.
Design: Seventy-six men (mean age, 51G1.0 years; body mass index, 32.8G0.5 kg/m2) were allocated to matched groups treated with isocaloric diets of HP (nZ34) or HC (nZ42). Outcome measures were weight, body composition, IGF-related peptides, homoeostasis model assessment of insulin resistance (HOMA1-IR) and adipokines.
Objective: To compare changes in the circulating IGF system following 12 weeks of moderate energy restriction (7000 kJ/day) in overweight or obese males on a high protein high red meat diet (HP) or a high carbohydrate diet (HC).
Results: Weight loss did not differ between diets (HP 8.5G0.6 kg; HC 8.2G0.6 kg, PO0.05). IGF-related peptides increased total IGF1 (HP 23%; HC 18%, P<0.0001), bioactive IGF1 (HP 18%; HC 15%, P<0.002), IGF1:IGF-binding protein-3 (IGFBP-3; HP 29%; HC 22%, P!0.0001) and IGFBP-1 (HP 24%; HC 25%, P<0.01). By contrast, decreases were observed in IGFBP-3 (HP K4%; HC K3%, P<0.01), pro-IGF2 (HP K3%; HC K6%, PZ0.001), total IGF2 (HP K7%; HC K3%, PZ0.001) and sIGF2R (HP K10%; HC K6%, P<0.005). Only IGFBP-2 increased differentially by diet (HP 34%; HC 50%, P<0.0001, diet P<0.05). Adiponectin increased in both diets, but leptin and HOMA-IR decreased (P<0.001).Damien P. Belobrajdic, Jan Frystyk, Nilani Jeyaratnaganthan, Ulrick Espelund, Allan Flyvbjerg, Peter M. Clifton and Manny Noake
Assessing the potential usefulness of IGF-related peptides and adiponectin for predicting disease risk
No full textCrown copyright © 2007 Published by Elsevier Ltd.OBJECTIVE: Insulin-like growth factors (IGF), their binding proteins and adiponectin have been investigated as potential blood-based biomarkers for a variety of diseases. Before these circulating proteins can be considered as biomarkers, their variation within and between individuals and between published studies must be critically assessed. The purpose of this study was to use the D-value to predict the potential usefulness of IGF-related peptides and adiponectin as biomarkers for the diagnosis of colorectal cancer (CRC). DESIGN: Intra- and inter-individual variation of total IGF-I and -II, IGF binding protein 1 (IGFBP-1), -2 and -3 and adiponectin, was examined in 10 healthy subjects over a 5 week period. This data was analysed in conjunction with previous publications to provide a D-value, which is a theoretical value that identifies the usefulness of the analyte individually and as a panel, as a biomarker for CRC. RESULTS: A single measurement of total IGF-I and -II, and adiponectin provided a reproducible representation of their circulating concentrations. The D-value for total IGF-II and IGFBP-3 were 0.5 and 0.47, respectively, which corresponded to area under the curve (AUC) values of 64 and 63%. Combining these analytes into a panel only slightly improved the D-value to 0.63 (AUC was 67%). CONCLUSIONS: Although serum levels of total IGF-I, total IGF-II and IGFBP-3 are stable and reproducible, the D-value calculations indicate that they have limited importance when used as biomarkers of CRC.Damien P. Belobrajdic, Ilka K. Priebe, Briony Forbes, Allan Flyvbjerg, Jian-Wen Chen, Leah J. Cosgrove, Jan Frystyk and Ian W. Saundershttp://www.elsevier.com/wps/find/journaldescription.cws_home/623041/description#descriptio
Determination of IGFs and their binding proteins
No full textThe worldwide clinical and scientific interest in peptides belonging to the insulin-like growth factor (IGF) system has brought along a call for standardization of assays used to quantify the different IGF related proteins. This relates in particular to the measurement of IGF-I, which has stood the test of time as an important biochemical tool in the diagnosis and treatment of growth hormone (GH) related disorders. The first international consensus statement on the measurement of IGF-I in 2011 represents an important milestone and will undoubtedly improve commutability of reference ranges for IGF-I and clinically applicable cut-off values. By contrast, there is no consensus addressing the measurements of the other IGF-related peptides. Nevertheless, measurement of these peptides may be of interest, either as additional tools in GH disorders or as prognostic biomarkers of various diseases. Therefore, standardization of assays for the other IGF-related peptides is highly relevant. This chapter discusses the recent consensus on IGF-I measurements and how this approach may be applied to measurement of the other IGF-related peptides. In addition, assay pitfalls, pre- and post-analytical challenges, alternative methods for IGF-I measurements and potential assays of tomorrow will be discussed.</p
Treatment with recombinant human insulin-like growth factor-1 improves growth in patients with PAPP-A2 deficiency
No full textContext: Pregnancy-associated plasma protein-A2 (PAPP-A2) is a metalloproteinase that specifically cleaves IGFBP-3 and IGFBP-5. Mutations in the PAPP-A2 gene have recently been shown to cause postnatal growth failure in humans, with specific skeletal features, due to the resulting decrease in IGF-1 bioavailability. However, a pharmacological treatment of this entity is yet to be established. Case Description: A 10.5-year-old girl and a 6-year-old boy, siblings from a Spanish family, with short stature due to a homozygous loss-of-function mutation in the PAPP-A2 gene (p.D643fs25.) and undetectable PAPP-A2 activity, were treated with progressive doses (40, 80, 100, and 120 mu;g/kg) of recombinant human IGF-1 (rhIGF-1) twice daily for 1 year. There was a clear increase in growth velocity and height in both siblings. Bioactive IGF-1 was increased, and spontaneous GH secretion was diminished after acute administration of rhIGF-1, whereas serum total IGF-1 and IGFBP-3 levels remained elevated. No episodes of hypoglycemia or any other secondary effects were observed during treatment. Conclusion: Short-term treatment with rhIGF-1 improves growth in patients with PAPP-A2 deficiency. (J Clin Endocrinol Metab 101: 3879-3883, 2016).Fil: Muñoz Calvo, María T.. Universidad Autónoma de Madrid; EspañaFil: Barrios, Vicente. Universidad Autónoma de Madrid; EspañaFil: Pozo, Jesús. Universidad Autónoma de Madrid; EspañaFil: Chowen, Julie A.. Universidad Autónoma de Madrid; EspañaFil: Martos-Moreno, Gabriel Á.. Universidad Autónoma de Madrid; EspañaFil: Hawkins, Federico. Universidad Complutense de Madrid; EspañaFil: Dauber, Andrew. Cincinnati Children's Hospital Medical Center; Estados UnidosFil: Domene, Horacio Mario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; ArgentinaFil: Yakar, Shoshana. New York University College of Dentistry; Estados UnidosFil: Rosenfeld, Ron G.. Oregon Health and Science University; Estados UnidosFil: Pérez-Jurado, Luis A.. Universitat Pompeu Fabra; EspañaFil: Oxvig, Claus. University Aarhus; DinamarcaFil: Frystyk, Jan. University Aarhus; DinamarcaFil: Argente, Jesús. Universidad Autónoma de Madrid; Españ
Learning Email Filtering Rules with Magi - A Mail Agent Interface
No full textAs the volume of data on the Internet increases the need for better tools to handle this flood of data is also growing. Interface agents are tools which are designed to aid the user in using various applications. This project describes the development of an agent which employs machine learning techniques to discover rules for filtering email. It explains how the agent observes the user in handling mail and how these observations are used to help automate this task. The agent is then evaluated, through testing, to examine whether such a tool can be useful as a personal assistant. A description of existing work is given, along with the design rationale, and a number of future extensions are suggested
Free insulin-like growth factors (IGF-I and IGF-II) in human serum
No full textAbstractUsing ultrafiltration by centrifugation we have isolated the free, unbound fractions of insulin-like growth factor I and II (free IGF-I and IGF-II) in human serum. In this way near in vivo conditions could be maintained before and during isolation. The recovery was 80 to 100% in the ultrafiltrates, which contained no detectable amounts of IGF-binding proteins (IGFBPs) as measured by Western ligand blotting and IGFBP-1 and IGFBP-3 immunoassays. The concentration of free peptides was measured in two ultrasensitive non-competitive IGF-I and IGF-II time-resolved fluoroimmunoassays. We found that (i) equilibrium between free and protein-complexed IGF was strongly dependent on re-establishment of in vivo conditions (temperature, pH, ionic milieu and dilution); (ii) metabolic events (glucose load and fasting) caused significant changes in free IGF-I and IGF-II levels without concomitant changes in total circulating levels of IGFs; (iii) in 49 healthy adult subjects (20 to above 60 years) free IGF-I was inversely related to age and ranged from 950 ± 150 ng/l (mean ± S.E.M.) (20–30 years) to 410 ± 70 ng/l (⪢ 60 years). The relative percentage was, however, unchanged, being 0.38 ± 0.02% of total IGF-I. In contrast, free IGF-II was independent of age, being 1,480 ± 80 ng/l (∼0.20 ± 0.01% of total IGF-II)
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