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

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.