Abstract
AimsRoux-en-Y gastric bypass (RYGB) is one of the most effective surgical therapies for the rapid resolution of type 2 diabetes. However, the mechanisms underlying the entero-hormonal response after surgery and the role of peptide tyrosine tyrosine (PYY) in the restoration of normoglycemia are still not clear.MethodsWe reproduced the RYGB technique in Wistar and Goto–Kakizaki rats and performed serum hormonal, histological, and hormonal-infusion test.ResultsUsing the diabetic Goto–Kakizaki (GK) rat model, we demonstrated that PYY plasma levels showed a remarkable peak approximately 30 min earlier than GLP-1 or GIP after mixed-meal administration in RYGB-operated rats with PYY. The GLP-1 and GIP areas under the curve (AUCs) increased after RYGB in GK rats. Additionally, the findings suggested that PYY (3-36) infusion led to increased GLP-1 and GIP plasma levels close to those obtained after a meal. Finally, the number of GLP-1-positive cells appeared to increase in the three segments of the small intestine in GK-RYGB-operated rats beyond the early presence of nutrient stimulation in the ileum. Nevertheless, PYY-positive cell numbers appeared to increase only in the ileum.ConclusionAt least in rats, these data demonstrate an earlier essential role for PYY in gut hormone regulation after RYGB. We understand that PYY contributes to GLP-1 and GIP release and there must be the existence of enteroendocrine communication routes between the distal and proximal small intestine.
Highlights
The effect of bariatric surgery on type 2 diabetes (T2DM) has generated considerable attention from the researchUniversity of Cadiz, Cadiz, Spain 4 Department of Human Anatomy and Embryology, Faculty of Medicine, University of Cadiz, Plaza Fragela s/n, 11003 Cadiz, Spain 5 Sustainable Social Development Research Institute (INDESS), University of Cadiz, Cadiz, Spain 6 Operative Statistic and Research Department, University of Cadiz, Cadiz, Spain community
Roux-en-Y gastric bypass (RYGB) is known as one of the most effective methods for maintaining body weight and improving glycemic control compared to medical therapy alone [1], but the underlying mechanism that leads to T2DM resolution remains controversial
We know that RYGB promotes substantial changes in the secretion of gut hormones, such as gastric inhibitory polypeptide (GIP) or mainly glucagon-like peptide-1 (GLP-1), an incretin hormone released postprandially by L cells from the ileum into the bloodstream
Summary
An oral glucose tolerance test (OGTT) was performed in Wistar, GK-RYGB, GK, and GK-sham 12-h fasting rats. To test whether the improved glucose tolerance was related to changes in incretin secretion, GLP-1 GIP and PYY plasma levels were assayed after mixed-meal administration in the four study groups 4 weeks after surgery. To test the role of PYY in stimulating GIP and GLP-1 secretion, a pool of GK-RYGB rats was randomly divided into three groups 4 weeks after surgery and fasted for 12 h. In this oral test, grouped animals were fed with mixed meal, infused. Statistical differences were determined between the AUC of the GK-RYGB+meal group versus the AUC of the GK-RYGB+ vehicle group; no differences were found versus the AUC of the GK-RYGB+PYY (3-36) group (P < 0.05) (Fig. 6d)
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