We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
GIP Receptor Agonism Attenuates GLP-1 Receptor Agonist-Induced Nausea and Emesis in Preclinical Models.
- Authors
Borner, Tito; Geisler, Caroline E.; Fortin, Samantha M.; Cosgrove, Richard; Alsina-Fernandez, Jorge; Dogra, Mridula; Doebley, Sarah; Sanchez-Navarro, Marcos J.; Leon, Rosa M.; Gaisinsky, Jane; White, Arianna; Bamezai, Ankur; Ghidewon, Misgana Y.; Grill, Harvey J.; Crist, Richard C.; Reiner, Benjamin C.; Ai, Minrong; Samms, Ricardo J.; De Jonghe, Bart C.; Hayes, Matthew R.
- Abstract
Glucagon-like peptide 1 receptor (GLP-1R) agonists decrease body weight and improve glycemic control in obesity and diabetes. Patient compliance and maximal efficacy of GLP-1 therapeutics are limited by adverse side effects, including nausea and emesis. In three different species (i.e., mice, rats, and musk shrews), we show that glucose-dependent insulinotropic polypeptide receptor (GIPR) signaling blocks emesis and attenuates illness behaviors elicited by GLP-1R activation, while maintaining reduced food intake, body weight loss, and improved glucose tolerance. The area postrema and nucleus tractus solitarius (AP/NTS) of the hindbrain are required for food intake and body weight suppression by GLP-1R ligands and processing of emetic stimuli. Using single-nuclei RNA sequencing, we identified the cellular phenotypes of AP/NTS cells expressing GIPR and GLP-1R on distinct populations of inhibitory and excitatory neurons, with the greatest expression of GIPR in γ-aminobutyric acid-ergic neurons. This work suggests that combinatorial pharmaceutical targeting of GLP-1R and GIPR will increase efficacy in treating obesity and diabetes by reducing nausea and vomiting.
- Subjects
VOMITING; GLUCAGON-like peptide 1; GLYCEMIC control; NAUSEA; ANIMAL models in research; CELL populations; LEPTIN; GASTRIC inhibitory polypeptide; FOOD habits; RESEARCH; BODY weight; ANIMAL experimentation; RESEARCH methodology; CELL receptors; EVALUATION research; RATS; COMPARATIVE studies; RESEARCH funding; MAMMALS; MICE
- Publication
Diabetes, 2021, Vol 70, Issue 11, p2545
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db21-0459