Electrical and Mechanical Stimulation of the Duodenum Increases GLP-1 Levels
6/9/2012 11:30:00 AM
6/9/2012 1:30:00 PM
, ADAM DUNKI-JACOBS, JOYCE SORRELL, RANDY J.. SEELEY, DAVID A.. D'ALESSIO,
Increases in GLP-1 are proposed to serve as a negative feedback signal for postprandial changes in gastric emptying and/or motility. Previous
data suggested that direct electrical stimulation (E-stim) of intestinal L-cells increases release of GLP-1. This suggests potential feed-forward increases in GLP-1 driven by intestinal neuronal and/or motor activity. To determine if E-stim could increase GLP-1 levels in an in vivo setting, we studied male Long Evans rats (300-350g) under general anesthesia. The peritoneal cavity was opened and two ~1cm long electrode cuffs were placed around the outside of the duodenum, 2cm distal to the pylorus, or around the ileum, 4 cm proximal to the cecum. A catheter was placed after the electrodes for nutrient infusion (3ml) of a mixed liquid diet (Ensure). Each animal had two 30min back to back experimental periods. The 1
30min consisted of either direct intestinal E-stim or nutrient infusion. During the 2
30min period all animals had a combination of E-stim plus nutrient infusion. In both the ileum and duodenum, nutrient infusion alone, but not E-stim alone, significantly increased plasma GLP-1 levels (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). E-stim could be increasing GLP-1 via increased intestinal muscle activity. Therefore, in another series of experiments we studied the impact of extra-luminal mechanical manipulation (M-stim) on GLP-1 levels. In the duodenum, but not the ileum, M-stim plus nutrient infusion also significantly increased GLP-1 over nutrient infusion or M-stim alone (p<0.05). Thus, E- and M-stim of the duodenum, and E-stim of the ileum augment nutrient-stimulated GLP-1 release. Future studies are aimed at determining whether E-stim-induced changes in neuronal activation and/or intestinal motility are the mechanism(s) by which E-stim increases in GLP-1.
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