Transient, early release of glucagon-like peptide-1 during low rates of intraduodenal glucose delivery

Context: The "incretin" hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), account for some 60% of the stimulation of insulin by oral glucose, but the determinants of their secretion from the small intestine are poorly understood. Cells which release GIP (K cells) are localized to the proximal small intestine, while GLP-1 releasing cells (L cells) predominate in the distal gut. It has been suggested that a threshold rate of duodenal glucose delivery (∼ 1.8 kcal/min) needs to be exceeded for stimulation of GLP-1. Objective: To determine whether a low intraduodenal glucose load (1 kcal/min) has the capacity to stimulate GLP-1, and if so, the characteristics of the response. Design: Retrospective analysis of all studies in our laboratory involving healthy humans administered intraduodenal glucose at 1 kcal/min for 120 min. Setting: Clinical research laboratory. Participants: 27 healthy subjects (24 male; age 36 ± 3 years; BMI 25.2 ± 0.7 kg/m²). Main outcome measures: Plasma GLP-1, GIP, insulin, and blood glucose concentrations, reported as mean ± SEM. Results: During intraduodenal glucose, plasma GLP-1 increased at 15 and 30 min (P < 0.001 for both) and returned to baseline thereafter. In contrast, there were sustained increases in plasma GIP (P < 0.001), insulin (P < 0.001), and blood glucose (P < 0.001). Conclusion: In healthy subjects, there is early, transient stimulation of GLP-1 by glucose loads hitherto believed to be "sub-threshold". The mechanisms underlying this effect, which could be attributed to initially rapid transit to jejunal L cells, or a duodeno-jejunoileal neural or hormonal loop, remain to be determined.