Protein-rich meals stimulate secretion of insulin, glucagon, and pancreatic polypeptide (PP) from the endocrine pancreas. On the one hand, this is due to increased levels of circulating amino acids, and, on the other, neural and/or endocrine factors can contribute to activation of islet cell function. The present study was designed to determine, first, pancreatic endocrine function and postprandial amino acid levels after a protein and a protein-carbohydrate meal and second, insulin, glucagon, and PP levels during infusion of amino acid mixtures that imitate the postprandial amino acid pattern. In healthy volunteers the ingestion of a protein-rich meal (300 g tenderloin steak) elicited within 1 h an increase of virtually all amino acids by 20-400 mumol/L above basal values. The infusion of two different amino acid solutions available for use in humans showed that Aminosteril-N-Hepa (AS) was better for the imitation of the so-called "insulinogenic" amino acids while Aminoplasmal L-10 (AP) gave more comparable plasma levels of the "glucagonogenic" amino acids. Both solutions were not able to imitate the postprandial amino acid pattern completely. With regard to insulin levels, both solutions gave a comparable increase, while AP but not AS stimulated glucagon and PP levels. This suggests that circulating amino acids may be responsible for 60% of the postprandial insulin response after a protein meal, while their contribution to glucagon release can only be roughly estimated at 30-60%. The contribution of circulating nutrients to the greater insulin response after the protein-carbohydrate meal was comparable (60%), while the attenuated glucagon response can be ascribed almost completely to the effect of circulating nutrients. In conclusion, the present data demonstrate that the composition of amino acid mixtures is as yet not ideal for a complete imitation of the postprandial amino acid pattern. The insulin, glucagon, and PP response depends on the amino acid mixtures and accordingly the respective plasma amino acid concentrations obtained during infusion studies. The adequate imitation of plasma amino acid levels is of critical importance for the evaluation of absorbed and circulating amino acid effects in the postprandial state.