| Literature DB >> 24049729 |
Keval Chandarana1, Cigdem Gelegen, Elaine E Irvine, Agharul I Choudhury, Chloé Amouyal, Fabrizio Andreelli, Dominic J Withers, Rachel L Batterham.
Abstract
The effect of peptide tyrosine-tyrosine (PYY) on feeding is well established but currently its role in glucose homeostasis is poorly defined. Here we show in mice, that intraperitoneal (ip) injection of PYY3-36 or Y2R agonist improves nutrient-stimulated glucose tolerance and enhances insulin secretion; an effect blocked by peripheral, but not central, Y2R antagonist administration. Studies on isolated mouse islets revealed no direct effect of PYY3-36 on insulin secretion. Bariatric surgery in mice, enterogastric anastomosis (EGA), improved glucose tolerance in wild-type mice and increased circulating PYY and active GLP-1. In contrast, in Pyy-null mice, post-operative glucose tolerance and active GLP-1 levels were similar in EGA and sham-operated groups. PYY3-36 ip increased hepato-portal active GLP-1 plasma levels, an effect blocked by ip Y2R antagonist. Collectively, these data suggest that PYY3-36 therefore acting via peripheral Y2R increases hepato-portal active GLP-1 plasma levels and improves nutrient-stimulated glucose tolerance.Entities:
Keywords: AUC, area under the curve; CNS, central nervous system; DPP-4, di-peptidyl peptidase-4; EGA, entero-gastric anastomosis; GLP-1; Glucose homeostasis; HFD, high-fat diet; ICV, intracerebroventricular; IPGTT, intraperitoneal glucose tolerance test; PYY; PYY, peptide tyrosine–tyrosine; T2DM, type 2 diabetes mellitus; WT, wild-type; Y2-receptor; Y2R, Y2-receptor; aCSF, artificial cerebrospinal fluid; active GLP-1, glucagon-like peptide-1(7-36)amide; ip, intraperitoneal
Year: 2013 PMID： 24049729 PMCID： PMC3773824 DOI： 10.1016/j.molmet.2013.03.001
Source DB: PubMed Journal: Mol Metab ISSN： 2212-8778 Impact factor: 7.422