Characterization of combined linagliptin and Y2R agonist treatment in diet-induced obese mice

Abstract Dipeptidyl peptidase IV (DPP-IV) inhibitors improve glycemic control by prolonging the action of glucagon-like peptide-1 (GLP-1). In contrast to GLP-1 analogues, DPP-IV inhibitors are weight-neutral. DPP-IV cleavage of PYY and NPY gives rise to PYY3-36 and NPY3-36 which exert potent anorect...

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Autores principales:	Henrik H. Hansen, Rikke V. Grønlund, Tamara Baader-Pagler, Peter Haebel, Harald Tammen, Leif Kongskov Larsen, Jacob Jelsing, Niels Vrang, Thomas Klein
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/97a3ac05b965484c814efcbeef1dbf0b
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spelling	oai:doaj.org-article:97a3ac05b965484c814efcbeef1dbf0b2021-12-02T14:27:53ZCharacterization of combined linagliptin and Y2R agonist treatment in diet-induced obese mice10.1038/s41598-021-87539-72045-2322https://doaj.org/article/97a3ac05b965484c814efcbeef1dbf0b2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87539-7https://doaj.org/toc/2045-2322Abstract Dipeptidyl peptidase IV (DPP-IV) inhibitors improve glycemic control by prolonging the action of glucagon-like peptide-1 (GLP-1). In contrast to GLP-1 analogues, DPP-IV inhibitors are weight-neutral. DPP-IV cleavage of PYY and NPY gives rise to PYY3-36 and NPY3-36 which exert potent anorectic action by stimulating Y2 receptor (Y2R) function. This invites the possibility that DPP-IV inhibitors could be weight-neutral by preventing conversion of PYY/NPY to Y2R-selective peptide agonists. We therefore investigated whether co-administration of an Y2R-selective agonist could unmask potential weight lowering effects of the DDP-IV inhibitor linagliptin. Male diet-induced obese (DIO) mice received once daily subcutaneous treatment with linagliptin (3 mg/kg), a Y2R-selective PYY3-36 analogue (3 or 30 nmol/kg) or combination therapy for 14 days. While linagliptin promoted marginal weight loss without influencing food intake, the PYY3-36 analogue induced significant weight loss and transient suppression of food intake. Both compounds significantly improved oral glucose tolerance. Because combination treatment did not further improve weight loss and glucose tolerance in DIO mice, this suggests that potential negative modulatory effects of DPP-IV inhibitors on endogenous Y2R peptide agonist activity is likely insufficient to influence weight homeostasis. Weight-neutrality of DPP-IV inhibitors may therefore not be explained by counter-regulatory effects on PYY/NPY responses.Henrik H. HansenRikke V. GrønlundTamara Baader-PaglerPeter HaebelHarald TammenLeif Kongskov LarsenJacob JelsingNiels VrangThomas KleinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Henrik H. Hansen Rikke V. Grønlund Tamara Baader-Pagler Peter Haebel Harald Tammen Leif Kongskov Larsen Jacob Jelsing Niels Vrang Thomas Klein Characterization of combined linagliptin and Y2R agonist treatment in diet-induced obese mice
description	Abstract Dipeptidyl peptidase IV (DPP-IV) inhibitors improve glycemic control by prolonging the action of glucagon-like peptide-1 (GLP-1). In contrast to GLP-1 analogues, DPP-IV inhibitors are weight-neutral. DPP-IV cleavage of PYY and NPY gives rise to PYY3-36 and NPY3-36 which exert potent anorectic action by stimulating Y2 receptor (Y2R) function. This invites the possibility that DPP-IV inhibitors could be weight-neutral by preventing conversion of PYY/NPY to Y2R-selective peptide agonists. We therefore investigated whether co-administration of an Y2R-selective agonist could unmask potential weight lowering effects of the DDP-IV inhibitor linagliptin. Male diet-induced obese (DIO) mice received once daily subcutaneous treatment with linagliptin (3 mg/kg), a Y2R-selective PYY3-36 analogue (3 or 30 nmol/kg) or combination therapy for 14 days. While linagliptin promoted marginal weight loss without influencing food intake, the PYY3-36 analogue induced significant weight loss and transient suppression of food intake. Both compounds significantly improved oral glucose tolerance. Because combination treatment did not further improve weight loss and glucose tolerance in DIO mice, this suggests that potential negative modulatory effects of DPP-IV inhibitors on endogenous Y2R peptide agonist activity is likely insufficient to influence weight homeostasis. Weight-neutrality of DPP-IV inhibitors may therefore not be explained by counter-regulatory effects on PYY/NPY responses.
format	article
author	Henrik H. Hansen Rikke V. Grønlund Tamara Baader-Pagler Peter Haebel Harald Tammen Leif Kongskov Larsen Jacob Jelsing Niels Vrang Thomas Klein
author_facet	Henrik H. Hansen Rikke V. Grønlund Tamara Baader-Pagler Peter Haebel Harald Tammen Leif Kongskov Larsen Jacob Jelsing Niels Vrang Thomas Klein
author_sort	Henrik H. Hansen
title	Characterization of combined linagliptin and Y2R agonist treatment in diet-induced obese mice
title_short	Characterization of combined linagliptin and Y2R agonist treatment in diet-induced obese mice
title_full	Characterization of combined linagliptin and Y2R agonist treatment in diet-induced obese mice
title_fullStr	Characterization of combined linagliptin and Y2R agonist treatment in diet-induced obese mice
title_full_unstemmed	Characterization of combined linagliptin and Y2R agonist treatment in diet-induced obese mice
title_sort	characterization of combined linagliptin and y2r agonist treatment in diet-induced obese mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/97a3ac05b965484c814efcbeef1dbf0b
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Characterization of combined linagliptin and Y2R agonist treatment in diet-induced obese mice

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