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

Obes Surg. 2020 Feb;30(2):697-706. doi: 10.1007/s11695-019-04239-y.

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-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.

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.

Keywords: Bariatric surgery; Enteroinsular axis; Glucagon-like peptide-1; Insulin secretion; Peptide hormones; Peptide tyrosine tyrosine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Experimental / blood*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / surgery*
  • Gastric Bypass*
  • Gastrointestinal Hormones / blood
  • Gastrointestinal Hormones / metabolism
  • Glucose Tolerance Test
  • Glycemic Control
  • Insulin Secretion / drug effects
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Intestines / drug effects
  • Intestines / pathology
  • Male
  • Peptide YY / blood
  • Peptide YY / pharmacology
  • Peptide YY / physiology*
  • Rats
  • Rats, Wistar
  • Weight Gain / drug effects

Substances

  • Blood Glucose
  • Gastrointestinal Hormones
  • Peptide YY