The Leading Role of Peptide Tyrosine Tyrosine in Glycemic Control After Roux-en-Y Gastric Bypass in Rats

Abstract

Aims Roux-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. Methods We reproduced the RYGB technique in Wistar and Goto-Kakizaki rats and performed serum hormonal, histological, and hormonal-infusion test. Results Using 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-1positive 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. Conclusion At 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.

Differential effects of RYGB surgery and best medical treatment for obesity-diabetes on intestinal and islet adaptations in obese-diabetic ZDSD rats

“…We also observed a significant increase in PYY tissue content in the ileum after RYGB compared to sham. These observations are broadly consistent with previous studies [ 76 ] and the demonstration of elevated post-prandial PYY with peak concentrations which precede those of GLP-1 [ 20 , 76 , 88 – 91 ]. However, observations with PYY and NPY2 receptor null mice have been less convincing regarding involvement of PYY in the positive effects of RYGB surgery [ 22 , 92 ].…”

“…However, ileal GLP-1 tissue content was decreased with BMT, whereas it was significantly increased following RYGB surgery. This accords with recent studies reporting increased numbers of GLP-1 positive cells in the ileum, duodenum, jejunum as well as gastric mucosa of rats after RYGB surgery [ 76 , 97 , 98 ]. Like PYY, studies using GLP-1 receptor knockout or exendin (9–39) have presented varying results on whether GLP-1 is a key mediator of the metabolic benefits in RYGB, calling for further exploration [ 42 , 99 – 101 ].…”

“…In contrast, GIP content was significantly decreased in the ileum of the BMT group. Consistent with our study, GIP positive cells have been reported to be unchanged in the rat ileum following RYGB [ 76 ]. Interestingly, Zhou et al [ 102 ] found that GIP was selectively decreased in the Roux limb but not in the other surgical limb possibly due to differences in exposure to undigested nutrients, reflecting the unavailability of bile acids and pancreatic enzymes which play key roles in the digestion and absorption of carbohydrate, protein and fat.…”

A short review on the features of the non-obese diabetic Goto-Kakizaki rat intestine

“…The surgical procedures performed on GK rats include the Roux-en-Y gastric bypass, duodenal-jejunal bypass, ileal transposition, and sleeve gastrectomy. Most studies reported that these surgeries improve glucose tolerance, reduce IR, alter plasma hormone (e.g., incretins) levels, and/or impair insulin signaling and response ( 45 - 47 ).…”

Sleeve Gastrectomy and Roux-En-Y Gastric Bypass. Two Sculptors of the Pancreatic Islet

“…Changes in energy homeostasis and body fat mass have been proposed as a primary mechanism to explain these phenomena [ 3 , 4 ], but other mechanisms such as changes in several gastrointestinal hormones also seem to be involved with a large number of publications written on the topic. Many of them have related the anatomical changes in the gastrointestinal tract after surgery with the modification of serum levels of glucagon like peptide-1 (GLP-1) [ 5 ], ghrelin [ 6 ], peptide tyrosine-tyrosine (PYY) [ 7 ], gastrointestinal inhibitory peptide (GIP) [ 8 ], or even leptin [ 9 ], among others, in humans and animal models. Their involvement is clear, but the exact mechanisms and their degree of participation remain partially unknown.…”