Regional specificity of the gut-incretin response to small intestinal glucose infusion in healthy older subjects

Abstract

The importance of the region, as opposed to the length, of small intestine exposed to glucose in determining the secretion of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) remains unclear. We sought to compare the glycemic, insulinemic and incretin responses to glucose administered to the proximal (12–60cm beyond the pylorus), or more distal (>70cm beyond the pylorus) small intestine, or both. 10 healthy subjects (9M,1F; aged 70.3±1.4years) underwent infusion of glucose via a catheter into the proximal (glucose proximally; GP), or distal (glucose distally; GD) small intestine, or both (GPD), on three separate days in a randomised fashion. Blood glucose, serum insulin and plasma GLP-1, GIP and CCK responses were assessed. The iAUC for blood glucose was greater in response to GPD than GP (P<0.05), with no difference between GD and GP. GP was associated with minimal GLP-1 response (P=0.05), but substantial increases in GIP, CCK and insulin (P<0.001 for all). GPD and GD both stimulated GLP-1, GIP, CCK and insulin (P<0.001 for all). Compared to GP, GPD induced greater GLP-1, GIP and CCK responses (P<0.05 for all). Compared with GPD, GD was associated with greater GLP-1 (P<0.05), but reduced GIP and CCK (P<0.05 for both), responses. We conclude that exposure of glucose to the distal small intestine appears necessary for substantial GLP-1 secretion, while exposure of both the proximal and distal small intestine result in substantial secretion of GIP.