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New metabolic interdependencies revealed by plasma metabolite profiling after two dietary challenges

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Abstract

Oral glucose tolerance tests (OGTT) are valuable tools for diagnosis of impaired glucose tolerance and insulin resistance. Protein intake modulates insulin secretion and sensitivity and thereby can alter the metabolic response. To assess these effects in the plasma metabolome, 15 healthy human volunteers underwent in random order an OGTT with and without 30 g of a protein-hydrolysate (OGTT + PL) followed by metabolite profiling via LC–MS/MS. Compared to the OGTT alone, plasma glucose response was reduced and insulin clearance retarded after OGTT + PL while suppression of catabolic markers such as free fatty acids, glycerol, lactate or acylcarnitines showed no difference between the two challenges. Clusters of plasma amino acids characterized by subgroups with similar physico-chemical characteristics revealed long-lasting declines after the OGTT and coherent increases after the OGTT + PL despite the fact that the protein-hydrolysate provided different amounts of individual amino acids. The amino acid clusters identified appear to derive from common transport processes involved in intestinal absorption and the insulin-dependent extraction by target tissues and suggest that these processes may be of high diagnostic value to assess insulin sensitivity.

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Acknowledgments

We specifically would like to thank Kerstin Geillinger for the insulin measurements, Manuela Sailer for the measurements of phospholipids and acylcarnitines. We also acknowledge Johanna Welzhofer and Manuela Hubersberger for their excellent technical assistance. GLP-1 was kindly measured by Jens Holst, University of Copenhagen, Denmark. This work was supported in part by the Else Kröner-Fresenius-Foundation, Bad Hombrug v.d. Höhe, Germany.

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The authors declare that they have no conflict of interest.

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Correspondence to Hannelore Daniel.

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Thomas Skurk and Isabel Rubio-Aliaga contributed equally to this work.

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Figure S1

Time–course profiling of the amino acids considering insulin extraction. In black, the fold-change time–course of the amino acids after a glucose and a protein-hydrolysate load (OGTT-PL). In grey, the calculated fold-change time–course by removing the clearance effect caused by insulin, i.e. the time–course due only to the protein-hydrolysate load added (PLcalculated). The calculation was performed for each variable and individual, as FCtime = i;treatment = PL = FCtime = i;treatment = OGTT + PL +( 1 – FCtime = i;treatment = OGTT). Data depicted as mean ± SEM (TIFF 773 kb)

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Skurk, T., Rubio-Aliaga, I., Stamfort, A. et al. New metabolic interdependencies revealed by plasma metabolite profiling after two dietary challenges. Metabolomics 7, 388–399 (2011). https://doi.org/10.1007/s11306-010-0258-z

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