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Knacke, H.* ; Pietzner, M.* ; Do, K.T. ; Römisch-Margl, W. ; Kastenmüller, G. ; Völker, U.* ; Völzke, H.* ; Krumsiek, J. ; Artati, A. ; Wallaschofski, H.* ; Nauck, M.* ; Suhre, K. ; Adamski, J. ; Friedrich, N.*

Metabolic fingerprints of circulating IGF-I and the IGF-I/IGFBP-3 ration: A multi-fluid metabolomics study.

J. Clin. Endocrinol. Metab. 101, 4730-4742:jc20162588 (2016)

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OBJECTIVE: Insulin-like Growth Factor (IGF-I) is known for its various physiological and severe pathophysiological effects on human metabolism, however underlying molecular mechanisms still remain unsolved. To reveal possible molecular mechanisms mediating these effects, for the first time we associated serum IGF-I levels with multi-fluid untargeted metabolomics data. METHODS: Plasma/urine samples of 995 non-diabetic participants of the Study of Health in Pomerania (SHIP-TREND) were characterized by mass spectrometry. Sex-specific linear regression analyses were performed to assess the association of IGF-I and IGF-I/IGFBP3 ratio with metabolites. Additionally, the predictive ability of the plasma and urine metabolome for IGF-I was assessed by OPLS analyses. RESULTS: and discussion: We revealed a multi-faceted image of associated metabolites with large sex differences. Confirming previous reports, we detected relations between IGF-I and steroid hormones or related intermediates. Furthermore, various associated metabolites were previously mentioned regarding IGF-I associated diseases, e.g. betaine and cortisol in cardiovascular disease and metabolic syndrome, lipid disorders and diabetes, or have previously been found to associate with differentiation and proliferation or mitochondrial functionality, e.g. phospholipids. Bradykinin, fatty acid derivatives and cortisol, which were inversely associated with IGF-I, might establish a link of IGF-I with inflammation. For the first time we showed an association between IGF-I and pipecolate, a metabolite linked to amino acid metabolism. Our study demonstrates that IGF-I action on metabolism is tractable even in healthy subjects and that the findings provide a solid basis for further experimental/clinical investigation, e.g. searching for inflammatory, cardiovascular disease or metabolic syndrome associated biomarkers and therapeutic targets.

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