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Journal of Gastrointestinal Surgery

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01-10-2009 | SSAT Plenary Presentation

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

Authors: Tammy L. Kindel, Stephanie M. Yoder, Randy J. Seeley, David A. D’Alessio, Patrick Tso

Published in: Journal of Gastrointestinal Surgery | Issue 10/2009

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.

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Title: Duodenal-Jejunal Exclusion Improves Glucose Tolerance in the Diabetic, Goto-Kakizaki Rat by a GLP-1 Receptor-Mediated Mechanism
Authors: Tammy L. Kindel
Stephanie M. Yoder
Randy J. Seeley
David A. D’Alessio
Patrick Tso
Publication date: 01-10-2009
Publisher: Springer-Verlag
Published in: Journal of Gastrointestinal Surgery / Issue 10/2009
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-009-0912-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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