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
Date
06/03/2009Pubmed ID
19488823DOI
10.1007/s11605-009-0912-9Scopus ID
2-s2.0-70350380343 (requires institutional sign-in at Scopus site) 100 CitationsAbstract
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.
Author List
Kindel TL, Yoder SM, Seeley RJ, D'Alessio DA, Tso PAuthor
Tammy Lyn Kindel MD, PhD Associate Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBariatric Surgery
Diabetes Mellitus, Type 2
Disease Models, Animal
Duodenum
Gastric Bypass
Glucagon-Like Peptide-1 Receptor
Glucose Intolerance
Ileum
Jejunum
Male
Rats
Rats, Wistar
Receptors, Glucagon
