Duodenal-jejunal Exclusion Improves Glucose Tolerance in the Diabetic, Goto-Kakizaki Rat by a GLP-1 Receptor-Mediated Mechanism

J Gastrointest Surg. 2009 Oct;13(10):1762-72. doi: 10.1007/s11605-009-0912-9. Epub 2009 May 12.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bariatric Surgery / methods*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / surgery
  • Disease Models, Animal
  • Duodenum / surgery*
  • Gastric Bypass
  • Glucagon-Like Peptide-1 Receptor
  • Glucose Intolerance / metabolism*
  • Glucose Intolerance / surgery
  • Ileum / surgery
  • Jejunum / surgery*
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, Glucagon / metabolism*

Substances

  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Receptors, Glucagon