GLP-1 mediated improvement of the glucose tolerance in the T2DM GK rat model after massive jejunal resection

Objective: The aim of this study was to clarify the role of the middle gut in the entero-pancreatic axis modification that leads to glucose improvement in the Goto-Kakizaki (GK) rat as a non-obese T2DM model. Background: Bariatric surgery is considered an assured solution for type 2 Diabetes (T2DM). Enterohormones such as ghrelin, gastric inhibitory polypeptide and mainly glucagon-like peptide-1 (GLP-1) were recognized as key players in the physiophathological mechanisms associated with entero-pancreatic axis regulation and glucose tolerance improvement. However, the influence of anatomical arrangements post-bariatric surgery on this axis is still debatable. Method: To this purpose, 50% of small intestine resections were performed on GK rats (n =6), preserving the proximal half of the jejunum and the ileum (IR50). Phenotypic and functional changes, such as performance in oral glucose tolerance tests, ileal release of GLP-1, beta-cell sensitivity to GLP-1, beta-cell mass, and turnover were characterized in IR50 and the surgical control group (Sham). Results: The glucose tolerance was improved and ileal release of GLP-1 was enhanced four weeks after IR50 versus the control group rats. Beta-cell mass, beta-cell proliferation, and beta-cell sensitivity to GLP-1 were also increased in the pancreas of 1R50 versus the control group rats. Conclusion: the jejunal exclusion increases beta-cell-mass and improves glucose tolerance by increasing in GLP-1 expression and number of receptors via the entero-pancreatic axis. (C) 2019 Elsevier GmbH. All rights reserved.