Sitagliptin and Roux-en-Y gastric bypass modulate insulin secretion via regulation of intra-islet PYY.

Details

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State: Public
Version: Final published version
Serval ID
serval:BIB_4709B9B33227
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Sitagliptin and Roux-en-Y gastric bypass modulate insulin secretion via regulation of intra-islet PYY.
Journal
Diabetes, obesity & metabolism
Author(s)
Guida C., McCulloch L.J., Godazgar M., Stephen S.D., Baker C., Basco D., Dong J., Chen D., Clark A., Ramracheya R.D.
ISSN
1463-1326 (Electronic)
ISSN-L
1462-8902
Publication state
Published
Issued date
03/2018
Peer-reviewed
Oui
Volume
20
Number
3
Pages
571-581
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The gut hormone peptide tyrosine tyrosine (PYY) is critical for maintaining islet integrity and restoring islet function following Roux-en-Y gastric bypass (RYGB). The expression of PYY and its receptors (NPYRs) in islets has been documented but not fully characterized. Modulation of islet PYY by the proteolytic enzyme dipeptidyl peptidase IV (DPP-IV) has not been investigated and the impact of DPP-IV inhibition on islet PYY function remains unexplored. Here we have addressed these gaps and their effects on glucose-stimulated insulin secretion (GSIS). We have also investigated changes in pancreatic PYY in diabetes and following RYGB.
Immunohistochemistry and gene expression analysis were used to assess PYY, NPYRs and DPP-IV expression in rodent and human islets. DPP-IV activity inhibition was achieved by sitagliptin. Secretion studies were used to test PYY and the effects of sitagliptin on insulin release, and the involvement of GLP-1. Radioimmunoassays were used to measure hormone content in islets.
PYY and DPP-IV localized in different cell types in islets while NPYR expression was confined to the beta-cells. Chronic PYY application enhanced GSIS in rodent and diabetic human islets. DPP-IV inhibition by sitagliptin potentiated GSIS; this was mediated by locally-produced PYY, and not GLP-1. Pancreatic PYY was markedly reduced in diabetes. RYGB strongly increased islet PYY content, but did not lead to full restoration of pancreatic GLP-1 levels.
Local regulation of pancreatic PYY, rather than GLP-1, by DPP-IV inhibition or RYGB can directly modulate the insulin secretory response to glucose, indicating a novel role of pancreatic PYY in diabetes and weight-loss surgery.
Keywords
Animals, Diabetes Mellitus, Type 2/physiopathology, Dipeptides/metabolism, Dipeptidyl Peptidase 4/metabolism, Dipeptidyl-Peptidase IV Inhibitors/pharmacology, Dose-Response Relationship, Drug, Female, Gastric Bypass, Glucagon-Like Peptide 1/metabolism, Humans, Hypoglycemic Agents/pharmacology, Insulin Secretion/physiology, Insulin-Secreting Cells/metabolism, Male, Mice, Rats, Wistar, Receptors, Neuropeptide Y/metabolism, Sitagliptin Phosphate/pharmacology, Roux-En-Y gastric bypass, dipeptidyl peptidase IV, glucagon-like peptide-1, insulin, islets, peptide tyrosine tyrosine
Pubmed
Web of science
Open Access
Yes
Create date
01/03/2018 11:14
Last modification date
20/08/2019 13:52
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