ArticleMolecular and cellular biology2014
A naturally occurring GIP receptor variant undergoes enhanced agonist-induced desensitization, which impairs GIP control of adipose insulin sensitivity.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- GIP as a Potential Therapeutic Target for Atherosclerotic Cardiovascular Disease-A Systematic Review.International journal of molecular sciences · 2020Pooled it
- Antidiabetic medications in the pipeline.Hormones (Athens, Greece) · 2026Review
- Glycemic and bodyweight effects ofScience advances · 2026Article
- GIP in Cardiovascular and Kidney Disease: From Physiology to Pharmacology.Diabetes, obesity & metabolism · 2026Review
- Interaction between fatty pancreas disease and genetically predicted glucose-dependent insulinotropic polypeptide on incident type 2 diabetes: evidence from the UK Biobank.Frontiers in endocrinology · 2026Article
- Review
- Glucagon-like Peptide-1 Receptor (GLP-1R) Signaling: Making the Case for a Functionally GInternational journal of molecular sciences · 2025Review
- Glucose-Dependent Insulinotropic Polypeptide in Incretin Physiology: Role in Health and Disease.Endocrine reviews · 2025Review
- What is the pipeline for future medications for obesity?International journal of obesity (2005) · 2025Review
- The role of GIPR in food intake control.Frontiers in endocrinology · 2025Review
- The C-terminal regions of the GLP-1 and GIP receptors are not the key determinants of their differential arrestin recruitment but modulate the rate of receptor endocytosis.Frontiers in pharmacology · 2025Article
- Does glucose-dependent insulinotropic polypeptide receptor blockade as well as agonism have a role to play in management of obesity and diabetes?The Journal of endocrinology · 2024Review
- The interplay of glucose-dependent insulinotropic polypeptide in adipose tissue.The Journal of endocrinology · 2024Review
- Pharmacological Advances in Incretin-Based Polyagonism: What We Know and What We Don't.Physiology (Bethesda, Md.) · 2024Review
- The Role of G Protein-Coupled Receptors and Receptor Kinases in PancreaticPharmacological reviews · 2024Review
- Mechanisms of action and therapeutic applications of GLP-1 and dual GIP/GLP-1 receptor agonists.Frontiers in endocrinology · 2024Review
- Tirzepatide, GIP(1-42) and GIP(1-30) display unique signaling profiles at two common GIP receptor variants, E354 and Q354.Frontiers in pharmacology · 2024Article
- Acute pharmacodynamic responses to exenatide: Drug-induced increases in insulin secretion and glucose effectiveness.Diabetes, obesity & metabolism · 2023Article
- Article
- Acute pharmacodynamic responses to exenatide: Drug-induced increases in insulin secretion and glucose effectiveness.medRxiv : the preprint server for health sciences · 2023Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Glucose-dependent insulinotropic polypeptide (GIP), an incretin hormone secreted from gastrointestinal K cells in response to food intake, has an important role in the control of whole-body metabolism. GIP signals through activation of the GIP receptor (GIPR), a G-protein-coupled receptor (GPCR). Dysregulation of this pathway has been implicated in the development of metabolic disease. Here we demonstrate that GIPR is constitutively trafficked between the plasma membrane and intracellular compartments of both GIP-stimulated and unstimulated adipocytes. GIP induces a downregulation of plasma membrane GIPR by slowing GIPR recycling without affecting internalization kinetics. This transient reduction in the expression of GIPR in the plasma membrane correlates with desensitization to the effects of GIP. A naturally occurring variant of GIPR (E354Q) associated with an increased incidence of insulin resistance, type 2 diabetes, and cardiovascular disease in humans responds to GIP stimulation with an exaggerated downregulation from the plasma membrane and a delayed recovery of GIP sensitivity following cessation of GIP stimulation. This perturbation in the desensitization-resensitization cycle of the GIPR variant, revealed in studies of cultured adipocytes, may contribute to the link of the E354Q variant to metabolic disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.