GIP receptor agonism blocks chemotherapy-induced nausea and vomiting.

Animals Rats Cisplatin / adverse effects Ferrets Nausea / chemically induced Vomiting / chemically induced Antineoplastic Agents / adverse effects
Antiemetic Chemotherapy Diabetes Incretin Obesity Vomiting

Journal

Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730

Informations de publication

Date de publication:
07 2023
Historique:
received: 10 03 2023
revised: 17 05 2023
accepted: 24 05 2023
medline: 27 6 2023
pubmed: 29 5 2023
entrez: 28 5 2023
Statut: ppublish

Résumé

Nausea and vomiting remain life-threatening obstacles to successful treatment of chronic diseases, despite a cadre of available antiemetic medications. Our inability to effectively control chemotherapy-induced nausea and vomiting (CINV) highlights the need to anatomically, molecularly, and functionally characterize novel neural substrates that block CINV. Behavioral pharmacology assays of nausea and emesis in 3 different mammalian species were combined with histological and unbiased transcriptomic analyses to investigate the beneficial effects of glucose-dependent insulinotropic polypeptide receptor (GIPR) agonism on CINV. Single-nuclei transcriptomics and histological approaches in rats revealed a topographical, molecularly distinct, GABA-ergic neuronal population in the dorsal vagal complex (DVC) that is modulated by chemotherapy but rescued by GIPR agonism. Activation of DVCGIPR neurons substantially decreased behaviors indicative of malaise in cisplatin-treated rats. Strikingly, GIPR agonism blocks cisplatin-induced emesis in both ferrets and shrews. Our multispecies study defines a peptidergic system that represents a novel therapeutic target for the management of CINV, and potentially other drivers of nausea/emesis.

Identifiants

DOI: 10.1016/j.molmet.2023.101743 PMID: 37245848 PMC: PMC10326744
pubmed: 37245848
pii: S2212-8778(23)00077-7
doi: 10.1016/j.molmet.2023.101743
pmc: PMC10326744
pii:
doi:

Substances chimiques

gastric inhibitory polypeptide receptor D6H00MV7K8
Cisplatin Q20Q21Q62J
Antineoplastic Agents 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

101743

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest MRH and BCR receive research funding from Boehringer Ingelheim and Novo Nordisk that were not used in support of these studies. MRH and BCDJ are CEO and CSO of Cantius Therapeutics, LLC that pursues biological work unrelated to the current study. RC, MA, and RJS are employees of Eli Lilly & Co. All other authors declare no competing interests.

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Auteurs

Tito Borner (T)

Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA, 19104, USA; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Benjamin C Reiner (BC)

Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Richard C Crist (RC)

Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

C Daniel Furst (CD)

Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Sarah A Doebley (SA)

Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Julia G Halas (JG)

Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Minrong Ai (M)

Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN, 46285, USA.

Ricardo J Samms (RJ)

Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN, 46285, USA.

Bart C De Jonghe (BC)

Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA, 19104, USA; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Matthew R Hayes (MR)

Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA, 19104, USA; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. Electronic address: hayesmr@pennmedicine.upenn.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › GIP receptor agonism blocks...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › GIP receptor agonism blocks...
questionsmedicales.fr › Produits chimiques inorganiques › Composés du platine › Cisplatine › GIP receptor agonism blocks...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Carnivora › Pinnipedia › Mustelidae › Furets › GIP receptor agonism blocks...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Signes et symptômes digestifs › Nausée › GIP receptor agonism blocks...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Signes et symptômes digestifs › Vomissement › GIP receptor agonism blocks...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › GIP receptor agonism blocks...