Duodenal-jejunal exclusion improves glucose tolerance in the diabetic, Goto-Kakizaki rat by a GLP-1 receptor-mediated mechanism.

Published

Journal Article

BACKGROUND: Gastric bypass results in the rapid resolution of type 2 diabetes. No causal evidence exists to link specific gut hormone changes with improvements in glucose homeostasis post-operatively. We hypothesized that surgical augmentation of the glucoregulatory factor GLP-1 would improve glucose tolerance in diabetic GK rats. We compared two procedures that increase distal small bowel stimulation, ileal interposition (IT), and duodenal-jejunal exclusion (DJE). METHODS: DJE, IT, DJE Sham, or IT Sham were performed in GK rats. Glucose tolerance was tested at 4 and 6 weeks, the latter with and without Exendin-[9-39], a GLP-1 receptor antagonist. Small bowel segments were harvested for GLP-1 protein content 2 weeks after DJE or Sham surgery. RESULTS: Despite similar weight profiles, a significant improvement in the OGTT was noted at 4 weeks after DJE and IT. Plasma GLP-1 levels were significantly elevated after DJE and IT. Intestinal GLP-1 was increased in the mid-jejunum and ileum after DJE. Exendin-[9-39] abolished the improvement in glucose tolerance after DJE. CONCLUSIONS: DJE increased GLP-1 secretion and improved glucose tolerance, an effect that was reversed by GLP-1 receptor antagonism. This study provides direct evidence that improvement of glucose tolerance following a gastric bypass-like surgery is mediated by enhanced GLP-1 action.

Full Text

Duke Authors

Cited Authors

  • Kindel, TL; Yoder, SM; Seeley, RJ; D'Alessio, DA; Tso, P

Published Date

  • October 2009

Published In

Volume / Issue

  • 13 / 10

Start / End Page

  • 1762 - 1772

PubMed ID

  • 19488823

Pubmed Central ID

  • 19488823

Electronic International Standard Serial Number (EISSN)

  • 1873-4626

Digital Object Identifier (DOI)

  • 10.1007/s11605-009-0912-9

Language

  • eng

Conference Location

  • United States