Background: Increases in L-cell release of GLP-1 are proposed to serve as a negative feedback signal for postprandial changes in gastric emptying and/or motility. Previous ex vivo data suggests that direct electrical stimulation (E-stim) of ileal segments stimulates secretion of GLP-1. This suggests potential feed-forward increases in GLP-1 driven by intestinal neuronal and/or motor activity.

Methods: To determine if E-stim could increase GLP-1 levels in an in vivo setting, we administered E-stim and nutrients to male Long- Evans rats (300-350 g) under general anesthesia.

Key results: Nutrient infusion into the duodenum or ileum significantly increased plasma GLP-1 levels, but E-stim applied to these locations did not (P < 0.05). However, the combination of E-stim and nutrient infusion, in either the ileum or duodenum, significantly increased plasma GLP-1 when compared to nutrient infusion alone (P < 0.05), and this effect was not blocked by either norepinephrine or atropine. To test the impact of intestinal motor activity, the effect of extra-luminal mechanical stimulation (M-stim) on GLP-1 levels was assessed. In the duodenum, but not the ileum, M-stim plus nutrient infusion significantly increased GLP-1 over nutrient infusion or M-stim alone (P < 0.05).

Conclusions & inferences: Thus, both E- and M-stim of the duodenum, but only E-stim of the ileum augmented nutrient-stimulated GLP-1 release. These data demonstrate that factors beyond enteral nutrients could contribute to the regulation of GLP-1 secretion.