Incretin effect after oral amino acid ingestion in humans.

Abstract

The incretin effect is the augmented insulin secretion by oral vs iv glucose at matching glucose levels. We previously demonstrated an augmented insulin secretion when fat is given orally rather than iv, suggesting an incretin effect also after fat. However, whether an incretin effect is also present after amino acid ingestion is not known. The objective of the study was to explore insulin secretion and incretin hormones after oral and iv amino acid administration at matched total amino acid concentrations in healthy subjects. An amino acid mixture (Vaminolac) was administered orally or iv at a rate resulting in matching total amino acid concentrations to 12 male volunteers with age 22.5 ± 1.4 years and a body mass index 22.4 ± 1.4 kg/m(2), who had no history of diabetes. Main outcome measures were area under the 120-minute curve for insulin, C-peptide, glucagon, intact and total glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and the insulin secretory rate and insulin clearance. Insulin, C-peptide, and glucagon levels increased after both oral and iv administration, but insulin secretion was 25% higher after oral than after iv amino acid challenges (P = .006), whereas there was no significant difference in the glucagon response. Intact and total GIP rose after oral but not after iv amino acid administration, whereas intact and total GLP-1 levels did not change significantly in either test. Oral amino acid mixture ingestion elicits a stronger insulin secretory response than iv amino acid at matching amino acid levels and this is associated with increased GIP level, suggesting that an incretin effect exists also after oral amino acids, possibly mediated by GIP.