A highly sensitive and specific assay for determination of IGF-I bioactivity in human serum

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Objective: Senescent changes in body composition and muscle strength are accompanied by reduced production of GH and IGF1, but the causal relationship remains elusive. We speculate that serum bioactive IGF1, measured by the IGF1 kinase receptor activation assay, is closer related to human physiological ageing than total IGF1 measured by immunoassay. Design: We conducted a cross-sectional study in 150 adult males and females, between 20 and 70 years. After an overnight fasting, serum levels of bioactive IGF1, total IGF1 and IGF-binding protein 1 (IGFBP1) and IGFBP3 were assessed. Furthermore, body composition and muscle strength was measured. Results: Total IGF1 levels were higher in females (PZ0.048). Bioactive IGF1 were identical in males and females (PZ0.31), decreasing with age. Total IGF1 tended to decrease more with age compared with bioactive IGF1 (K1.48 vs K0.89 percent/year, PZ0.052). Total body fat (TBF) was lower and BMI was higher in males (P!0.001 and PZ0.005), and both increased with age. Knee extension and elbow flexion force were higher in males (PZ0.001 and PZ0.001), but decreased with age in both genders.Total but not bioactive IGF1 was positively correlated to TBF, knee extension and muscle function in males. In multiple linear regression, only age predicted total IGF1, whereas age and IGFBP1 predicted bioactive IGF1. Conclusions: Bioactive IGF1 tends to decrease to a lesser extent than total IGF1 with age and was not correlated with measures of body composition or muscle strength. Therefore, levels of circulating bioactive IGF1 does not appear to be a better biomarker of physiological ageing than total IGF1.

Section: Methodsmentioning

confidence: 99%

“…phosphorylate) the IGF1 receptor (IGF1R) in vitro (i.e. bioactive IGF1) (21). Subsequent studies have demonstrated that bioactive IGF1 is inversely correlated with age (22), significantly higher in females compared with males (23), and positively correlated with IGF1 as measured by immunoassay (i.e.…”

Section: Introductionmentioning

confidence: 99%

Serum levels of bioactive IGF1 and physiological markers of ageing in healthy adults

Vestergaard

Hansen

Frystyk

et al. 2014

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“…Bioactive IGF1 was measured by the IGF1 kinase receptor activator assay based on human embryonic renal cells (EBNA 293) transfected with the human IGF1R gene (23). In brief, cultured cells were stimulated with either IGF1 standards or serum samples (diluted tenfold) from the subjects in this study.…”

Section: Biochemical Analysesmentioning

confidence: 99%

Moderate energy restriction-induced weight loss affects circulating IGF levels independent of dietary composition

Belobrajdic

Frystyk

Jeyaratnaganthan

et al. 2010

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Background: 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. 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). Design: Seventy-six men (mean age, 51G1.0 years; body mass index, 32.8G0.5 kg/m

“…Intra-and inter-assay coefficient of variation (CV) averaged 5 and 10% respectively (15). Bioactive IGF1 was determined by a cell-based kinase receptor activation assay (KIRA) based on human embryonic cells transfected with the human IGF1 receptor (IGF1R) gene (16). The bioassay determines the ability of serum IGF to phosphorylate the IGF1R in vitro, and takes into account the presence of the IGFBPs and their ability to modify IGF1R activation.…”

Section: Assaysmentioning

confidence: 99%

Conventional and novel biomarkers of treatment outcome in patients with acromegaly: discordant results after somatostatin analog treatment compared with surgery

Rubeck

Madsen²,

Andreasen³

et al. 2010

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Context: Control of disease activity in acromegaly is critical, but the biochemical definitions remain controversial. Objective: To compare traditional and novel biomarkers and health status in patients with acromegaly treated with either surgery alone or somatostatin analog (SA). Design and methods: Sixty-three patients in long-term remission based on normalized total IGF1 levels after surgery alone (nZ36) or SA (nZ27) were studied in a cross-sectional manner. The groups were comparable at diagnosis regarding demographic and biochemical variables. Each subject underwent 3 h of serum sampling including a 2-h oral glucose tolerance test (OGTT). Health status was measured by two questionnaires: EuroQoL and Acrostudy (Patient-assessed-Acromegaly symptom questionnaire (PASQ)). Results: Total and bioactive IGF1 (mg/l) levels were similar (total: 185G10 (SA) versus 171G8 (surgery) (PZ0.28); bioactive: 1.9G0.2 vs 1.9G0.1 (PZ0.70)). Suppression of total and free GH (mg/l) during OGTT was blunted in the SA group (total GH nadir : 0.59G0.08 (SA) versus 0.34G0.06 (surgery) (PZ0.01); free GH nadir : 0.43G0.06 vs 0.19G0.04 (P!0.01)). The insulin response to OGTT was delayed, and the 2-h glucose level was elevated during SA treatment (PZ0.02). Disease-specific health status was better in patients after surgery (PZ0.02). Conclusions: i) Despite similar and normalized IGF1 levels, SA treatment compared with surgery alone was associated with less suppressed GH levels and less symptom relief; ii) this discordance may be due to specific suppression of hepatic IGF1 production by SA; iii) we suggest that biochemical assessment during SA treatment should include both GH and IGF1.