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REVIEW article
Front. Endocrinol.
Sec. Diabetes: Molecular Mechanisms
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1532076
This article is part of the Research Topic The Impact of GIP/GIPR on Metabolic Diseases: How the Field Is Evolving View all 4 articles
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Glucose-dependent insulinotropic polypeptide (GIP) is one of two incretin hormones playing key roles in the control of food intake, nutrient assimilation, insulin secretion and whole-body metabolism. Recent pharmacological advances and clinical trials show that unimolecular co-agonists that target the receptors for the incretins -GIP and glucagon-like peptide 1 (GLP-1) -offer more effective treatment strategies for obesity and type 2 diabetes mellitus (T2D) compared with GLP-1 receptor (GLP1R) agonists alone, suggesting previously underappreciated roles of GIP in regulating food intake and body weight. The mechanisms by which GIP regulates energy balance remain controversial as both agonism and antagonism of the GIP receptor (GIPR) produce weight loss and improve metabolic outcomes in preclinical models. Recent studies have shown that GIPR signalling in the central nervous system (CNS), especially in regions of the brain that regulate energy balance, is essential for its action on appetite regulation. This finding has sparked interest in understanding the mechanisms by which GIP engages brain circuits to reduce food intake and body weight. In this review, we present key knowledge around the actions of GIP on food intake regulation and the potential mechanisms by which GIPR and GIPR/GLP1R agonists may regulate energy balance.
Keywords: GIP/GIPR, GLP1R, food intake, Body Weight, Central Nervous System, Obesity, diabetes
Received: 21 Nov 2024; Accepted: 25 Feb 2025.
Copyright: © 2025 James-Okoro, Lewis, Gribble and Reimann. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Frank Reimann, University of Cambridge, Cambridge, United Kingdom
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