Affinage

GIPR

Gastric inhibitory polypeptide receptor · UniProt P48546

Length
466 aa
Mass
53.2 kDa
Annotated
2026-06-10
100 papers in source corpus 38 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GIPR is a class B G protein-coupled receptor of the VIP/glucagon/secretin family that, upon binding glucose-dependent insulinotropic polypeptide (GIP), couples positively to Gs and elevates cAMP to control glucose homeostasis, energy balance, and adipose metabolism (PMID:8575774, PMID:8920677). In pancreatic beta cells GIPR potentiates glucose-stimulated insulin secretion through cAMP, and also engages a cAMP-independent, ERK-dependent cytoprotective program that upregulates TCF1/Tcf7 to promote beta-cell survival, a pathway not shared by GLP-1R (PMID:26642437, PMID:27422784). The receptor signals through both Gs/cAMP and β-arrestin 2, with β-arrestin 2 recruitment required for full biological activity and for endosomal Gs-mediated signaling, while exhibiting preferential plasma-membrane recycling, low internalization, and a pharmacology distinct from GLP-1R (PMID:36774542, PMID:38871982). Agonist exposure generates ligand-specific C-terminal serine phosphorylation signatures, and chronic agonism drives homologous functional desensitization in islets and adipocytes through a mechanism largely independent of internalization or β-arrestin recruitment (PMID:38091482, PMID:39788289, PMID:33020469). Beyond the islet, GIPR governs adipose insulin sensitization via enhanced white-adipose glucose disposal in a weight- and GLP-1R-independent manner, with WAT GIPR residing predominantly in pericytes and mesothelial cells rather than adipocytes (PMID:34003802, PMID:35192688). In the CNS, GIPR signaling—specifically in GABAergic neurons—is required for food-intake suppression, the anti-aversive effect, and the synergistic weight loss of dual GLP-1R/GIPR agonism, with brainstem area postrema and dorsal vagal complex circuits engaged, and agonism versus antagonism reducing body weight through mechanistically opposite routes (PMID:33571454, PMID:35499381, PMID:39612941, PMID:40301583). GIPR additionally drives adrenocortical steroidogenesis and, when ectopically expressed via somatic 19q13.32 rearrangements that juxtapose the locus with glucocorticoid response elements, causes food-dependent cortisol secretion in adrenal adenomas and GH secretion in somatotropinomas (PMID:22043004, PMID:28931750, PMID:30567927). Receptor activity is further modulated by N-terminus-altered splice variants that act as ligand-independent dominant-negative suppressors by occupying the ligand-binding pocket (PMID:37792509).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1995 High

    Establishing the molecular identity of GIPR as a seven-transmembrane GPCR of the secretin/glucagon family defined the receptor class and provided the gene structure required for all subsequent mechanistic work.

    Evidence cDNA cloning, gene isolation, and hydropathic analysis of the human gene

    PMID:8575774

    Open questions at the time
    • Did not define downstream coupling or ligand pharmacology
    • No tissue-specific functional role established
  2. 1996 High

    Demonstrating high-affinity GIP binding coupled to adenylate cyclase identified Gs-cAMP as the primary signaling output, the core mechanism of incretin action.

    Evidence Recombinant expression in CHO cells with radioligand binding and adenylate cyclase assay

    PMID:8920677

    Open questions at the time
    • cAMP-independent pathways not addressed
    • In vivo physiological consequences not tested
  3. 2011 High

    Linking GIPR to adrenal steroidogenesis via cAMP/ERK and steroidogenic gene induction extended receptor function beyond the islet and showed an essential role in basal corticosteroid production.

    Evidence Pharmacological activation in Y1 cells plus Gipr-/- mouse adrenal phenotyping

    PMID:22043004

    Open questions at the time
    • Physiological versus ectopic adrenal signaling not distinguished here
    • Compensatory ACTH receptor changes complicate interpretation
  4. 2015 High

    Identifying a cAMP-independent, ERK/TCF1 cytoprotective pathway distinguished GIPR from GLP-1R mechanistically and explained beta-cell survival effects.

    Evidence Beta-cell-specific Gipr KO mice, human islet TCF7 knockdown, ERK inhibition, apoptosis assays

    PMID:26642437

    Open questions at the time
    • Upstream coupling that bifurcates cAMP from ERK not resolved
    • Transcriptional targets of TCF1 in beta cells not fully mapped
  5. 2016 High

    CRISPR ablation confirming receptor-specific cAMP and GSIS potentiation in beta cells established GIPR as the obligate transducer of beta-cell GIP signaling.

    Evidence CRISPR/Cas9 disruption in INS-1 cells with cAMP/GSIS assays and in vivo anti-GIPR antibody validation

    PMID:27422784

    Open questions at the time
    • Did not address chronic desensitization
    • Human islet relevance addressed only later
  6. 2017 Medium

    Defining somatic 19q13.32 rearrangements that juxtapose GIPR with glucocorticoid response elements explained ectopic GIPR expression and food-dependent cortisol secretion in adrenal tumors.

    Evidence Methylation, chromosomal microarray, and allelic expression analysis of patient adenomas/hyperplasias

    PMID:28931750

    Open questions at the time
    • Mechanism in patients lacking detectable duplications unresolved
    • Single-lab patient cohort
  7. 2017 Medium

    Showing functional GIP/cAMP/GH coupling in somatotropinomas extended ectopic GIPR activity to the pituitary and linked GIP to growth hormone release.

    Evidence Primary somatotropinoma cultures with cAMP/GH assays and GIP promoter-luciferase reporter

    PMID:28179449

    Open questions at the time
    • Genomic basis of ectopic pituitary expression not defined
    • Limited primary tumor sample
  8. 2018 High

    Crystallographic mapping of an antagonist antibody onto the conserved hydrophobic GIP-binding residues defined the molecular interface for receptor blockade.

    Evidence Crystallography and competitive displacement assays of an anti-GIPR antibody

    PMID:30567927

    Open questions at the time
    • Full active-state structure not resolved here
    • Antibody-specific contacts may not generalize to peptide antagonists
  9. 2018 High

    Demonstrating that GIPR agonism lowers body weight by suppressing food intake, GIPR-dependently and GLP-1R-independently, established GIPR agonism as an anti-obesity mechanism.

    Evidence Chronic DIO dosing with Gipr-/- and Glp1r-/- models, pair-feeding, and indirect calorimetry

    PMID:30578168

    Open questions at the time
    • Site of anti-obesity action not localized in this study
    • Paradox with antagonist-mediated weight effects unresolved
  10. 2020 High

    Single-cell and lineage-targeting work relocated WAT GIPR to pericytes and mesothelial cells rather than adipocytes, revising the cellular substrate for adipose GIP action; resistin/c-Jun was shown to drive adipocyte GIPR transcription.

    Evidence Single-nucleus RNA-seq and multiple Cre-driver KO models; ChIP and Retn-/- adipocyte studies

    PMID:23002036 PMID:35192688

    Open questions at the time
    • Functional role of pericyte/mesothelial GIPR mechanistically unresolved
    • Reconciliation with adipocyte insulin-sensitization data incomplete
  11. 2020 High

    Showing chronic agonism desensitizes adipocyte GIPR and functionally mimics antagonism reframed how sustained GIPR engagement affects adipose responsiveness.

    Evidence Chronic agonist treatment with primary adipocyte cAMP assays and conditional adipocyte KO in DIO mice

    PMID:33020469

    Open questions at the time
    • Molecular basis of desensitization not defined here
    • Reconciliation of agonist versus antagonist weight effects unresolved
  12. 2020 Medium

    Establishing GIPR roles in neurite outgrowth, nerve regeneration, and bone-marrow hematopoietic gene regulation broadened the receptor's tissue physiology beyond metabolism.

    Evidence siRNA in cortical neurons; Gipr-/- sciatic nerve crush; bone-marrow KO/chimera with hematopoietic stressors

    PMID:19170165 PMID:32389828 PMID:33321289

    Open questions at the time
    • Downstream effectors incompletely defined
    • Physiological significance of modest hematopoietic changes unclear
  13. 2021 High

    CNS-specific and GABAergic-neuron-specific KO localized the food-intake and weight effects of GIPR agonism to GABAergic CNS neurons and tied them to dual-agonist synergy and anti-aversion.

    Evidence CNS-, GABAergic-, and glutamatergic-specific Gipr KO mice with pharmacology, cFos, and behavioral readouts

    PMID:33571454 PMID:35499381

    Open questions at the time
    • Identity of the specific GABAergic populations not fully resolved
    • Circuit connectivity to feeding centers incompletely mapped
  14. 2021 High

    Clamp and transcriptomic studies established weight-independent, GLP-1R-independent insulin sensitization via enhanced WAT glucose disposal and reduced circulating BCAAs.

    Evidence Tirzepatide/LAGIPRA in Glp-1r-null mice, hyperinsulinemic-euglycemic clamp, and adipose RNA-seq

    PMID:34003802

    Open questions at the time
    • Cellular site within adipose tissue not pinpointed here
    • Direct versus indirect insulin-sensitizing mechanism unresolved
  15. 2021 Medium

    Brainstem mapping placed the anti-nausea effect in the area postrema with Gipr/Npy2r co-expression, and co-receptor cell studies showed bispecific GIPR-block/GLP-1-activate molecules amplify endosomal cAMP.

    Evidence cFos and in situ hybridization in brainstem; cAMP and internalization imaging in co-expressing cells

    PMID:34095876 PMID:35499381

    Open questions at the time
    • Causal GIP-PYY interaction at single-neuron level not proven
    • Endosomal amplification shown only in recombinant cells
  16. 2021 Medium

    Structural modeling and mutagenesis defined activation-critical residues and a K293–E362 salt bridge, and demonstrated distinct binding modes of agonists versus truncated antagonists.

    Evidence Homology modeling, molecular dynamics, and site-directed mutagenesis with functional assays

    PMID:33891864

    Open questions at the time
    • Based on homology model rather than experimental structure
    • Single-lab predictions
  17. 2022 Medium

    Genetic studies revealed GIPR has anti-atherosclerotic/anti-inflammatory and immune-modulatory functions, including myeloid GIPR support of adipose type 2 immunity via S100A8/A9 and ACC analgesia via neuroinflammation suppression.

    Evidence Apoe-/-:Gipr-/- atherosclerosis model; LysM-Cre myeloid KO with S100a9 double KO; ACC shRNA/pharmacology with electrophysiology

    PMID:33717200 PMID:35712239 PMID:36055579

    Open questions at the time
    • Cell-of-origin for anti-atherosclerotic effect not fully resolved
    • Single-lab findings for each tissue
  18. 2023 High

    Human islet pharmacology established that tirzepatide acts through both incretin receptors in humans, whereas reduced mouse GIPR potency makes GLP-1R dominant in mice, clarifying species discrepancies.

    Evidence Human and mouse islet perifusion with selective GIPR antagonism and multi-hormone readouts

    PMID:37277609

    Open questions at the time
    • Molecular basis of species potency difference not resolved
    • Did not address chronic in vivo desensitization
  19. 2023 High

    Trafficking, phosphorylation, and structural studies defined GIPR's distinctive regulation: preferential recycling over GLP-1R, agonist-specific phosphosite signatures, and a splice-variant dominant-negative mechanism.

    Evidence Receptor trafficking imaging in beta cells; TIMS-TOF phosphosite mapping; cryo-EM of splice variants with functional assays

    PMID:36774542 PMID:37792509 PMID:38091482

    Open questions at the time
    • Functional consequence of each phosphosite not assigned
    • In vivo abundance and impact of splice variants not quantified
  20. 2024 High

    β-arrestin 2 was established as required for full GIPR activity and endosomal signaling, and a ligand-free GIPR-Gs cryo-EM structure revealed a transitional Gs-stabilized active intermediate.

    Evidence 47-variant pharmacology with human burden testing and β-arrestin 2 KO mice; cryo-EM of ligand-free GIPR-Gs complex

    PMID:38346960 PMID:38871982

    Open questions at the time
    • How β-arrestin shapes signaling given low internalization unresolved
    • Physiological occupancy of the ligand-free Gs intermediate unknown
  21. 2024 Medium

    Variant and cell-type-specific studies refined GIPR pharmacology in vivo: the Q354 variant alters trafficking and GIP sensitivity, and beta-cell Lepr+ GIPR mediates co-agonist glycemic benefit while GABAergic GIPR governs weight effects.

    Evidence GIPR-Q350 knock-in mice; Lepr-Cre and GABAergic/glutamatergic Gipr KO with co-agonist treatment; scRNA-seq

    PMID:37925022 PMID:38492844 PMID:39612941

    Open questions at the time
    • Mechanistic basis of trafficking-driven sensitivity change incomplete
    • Division between glycemic and weight effects across cell types not fully integrated
  22. 2025 High

    Comparative agonist/antagonist studies demonstrated mechanistically distinct weight-loss routes—agonism via GABAergic GIPR neurons and GLP-1R-independent, antagonism requiring functional GLP-1R—while chronic agonism causes homologous islet desensitization via an internalization/β-arrestin-independent mechanism.

    Evidence Multiple cell-type-specific KO models with snRNA-seq of dorsal vagal complex; live-cell cAMP imaging in islets with in vivo re-challenge; somatotroph GH3 signaling model

    PMID:39788289 PMID:40301583 PMID:41066443 PMID:41287212

    Open questions at the time
    • Molecular pathway producing GIPR desensitization without internalization unidentified
    • Unified model reconciling agonist and antagonist efficacy still incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • The central paradox of how both GIPR agonism and antagonism produce weight loss, and the precise molecular mechanism of internalization-independent desensitization, remain unresolved.
  • Effector mediating internalization/β-arrestin-independent desensitization unknown
  • Integrated model across CNS, islet, and adipose actions not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0048018 receptor ligand activity 2 GO:0060090 molecular adaptor activity 1
Localization
GO:0005768 endosome 3 GO:0005886 plasma membrane 3 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1430728 Metabolism 2
Partners
ARRB2GIPGLP1RGNASGRK2NPY2R

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 The human GIPR gene encodes a 466-amino acid G protein-coupled receptor with seven transmembrane domains, belonging to the VIP/glucagon/secretin receptor family. The gene spans ~13.8 kb, consists of 14 exons, and contains 17 Alu repeats. cDNA cloning, gene isolation, hydropathic analysis Genomics High 8575774
1996 The hamster GIP receptor (ortholog of human GIPR) expressed in CHO cells binds GIP with high affinity (IC50 = 9.6 nM) and is positively coupled to adenylate cyclase, establishing Gs-cAMP as the primary downstream signaling pathway. Recombinant expression in CHO cells, radioligand binding, adenylate cyclase assay Nihon rinsho. Japanese journal of clinical medicine High 8920677
2011 GIPR signaling in adrenocortical cells promotes steroidogenesis via cAMP elevation, ERK1/2 activation, upregulation of steroidogenic genes, and increased neutral lipid storage. Gipr-/- mice have reduced basal corticosterone but enhanced ACTH receptor expression and sensitivity, demonstrating that GIPR is essential for adrenal steroidogenesis. Pharmacological activation with [d-Ala2]GIP in Y1 adrenocortical cells; Gipr-/- mouse model; cAMP assay; ERK1/2 activation assay; gene expression analysis Diabetes High 22043004
2015 GIPR signaling in pancreatic beta cells promotes beta cell survival and function through a cAMP-independent, ERK-dependent pathway that upregulates TCF1 (encoded by Tcf7). Loss of beta-cell GIPR reduces TCF7 expression, impairs cytoprotective GIP responses, and enhances apoptosis. GLP-1 does not activate this TCF1 pathway. Beta-cell-specific Gipr knockout mice (MIP-Cre:Giprflox/flox); in vitro GIP/GLP-1 stimulation; ERK inhibition; TCF7 knockdown in human and mouse islets; apoptosis assays; insulin secretion measurement Nature medicine High 26642437
2016 GIPR activation in INS-1 pancreatic beta cells induces cAMP production and potentiates glucose-stimulated insulin secretion (GSIS). CRISPR/Cas9 ablation of GIPR abolishes GIP-stimulated cAMP and attenuates GSIS, confirming receptor-specific incretin signaling in beta cells. CRISPR/Cas9 gene disruption in INS-1 cells; cAMP assay; GSIS assay; in vivo validation in GLP-1R KO mice with anti-GIPR monoclonal antibody The Biochemical journal High 27422784
2017 Ectopic GIPR expression in GIP-dependent Cushing's syndrome adrenocortical adenomas occurs through monoallelic transcriptional activation, with somatic chromosome 19q13.32 duplications identified in a subset of patients. Rearrangement juxtaposes the GIPR locus with cis-acting glucocorticoid response elements, driving aberrant GIPR transcription. Molecular analyses of adrenocortical adenomas/hyperplasias from 15 patients; promoter methylation analysis; chromosomal microarray; allelic expression analysis JCI insight Medium 28931750
2017 In GIPR-expressing somatotropinomas, GIP stimulation increases GH secretion and cAMP production (higher Forskolin sensitivity), demonstrating functional GIP/GIPR coupling to GH release in a subset of gsp-negative pituitary tumors. IGF-1 (but not GH) also dose-dependently induces GIP promoter activity in enteroendocrine cells. Primary somatotropinoma cultures stimulated with GIP; cAMP/GH secretion assays; GIP promoter-luciferase reporter in STC-1 cells European journal of endocrinology Medium 28179449
2018 A human anti-GIPR antagonist antibody (hGIPR-Ab) displaces GIP and binds GIPR using the same conserved hydrophobic residues used by GIP itself, as revealed by crystallographic and mechanistic studies. Crystallography; competitive displacement assays; mechanistic binding studies Science translational medicine High 30567927
2018 Chronic treatment of DIO mice with GIPR agonists lowers body weight by reducing food intake (not by increasing energy expenditure), as established by pair-feeding studies and indirect calorimetry. This effect is absent in Gipr-/- mice and preserved in Glp1r-/- mice, confirming GIPR-selective action. Peptide-based GIPR antagonists did not lower body weight under comparable conditions. Chronic dosing in DIO mice; Gipr-/- and Glp1r-/- genetic models; pair-feeding; indirect calorimetry; in vitro receptor selectivity assays Molecular metabolism High 30578168
2020 Chronic GIPR agonism desensitizes GIPR in primary adipocytes (differentiated in vitro and in vivo adipose tissue), reducing cAMP responsiveness and functionally mimicking GIPR antagonism. Adipocyte GIPR activity is partially responsible for anti-GIPR antibody-mediated prevention of weight gain in DIO mice. Chronic GIP agonist treatment; cAMP assay in primary adipocytes; conditional GIPR adipocyte knockout mice; DIO model; muGIPR-Ab treatment Nature communications High 33020469
2020 GIP-GIPR signaling promotes neurite outgrowth of cortical neurons via an Akt-dependent mechanism that increases Rac1/Cdc42 phosphorylation. siRNA knockdown of GIPR in E18 neurons reduces neuritogenesis; exogenous GIP rescues axon extension. siRNA knockdown in E18 rat cortical neurons; GIP stimulation; Western blot for Rac1/Cdc42 phosphorylation; neurite length measurement Biochemical and biophysical research communications Medium 33321289
2021 CNS GIPR signaling is required for body weight reduction and food intake suppression by acyl-GIP and GLP-1/GIP co-agonism. CNS-specific Gipr KO mice show blunted or absent body weight loss in response to central and peripheral acyl-GIP. Acute GIP administration increases cFos neuronal activity in hypothalamic feeding centers. CNS-specific Gipr KO and humanized CNS-hGIPR deletion mice; central/peripheral acyl-GIP administration; cFos immunohistochemistry; body weight/food intake measurement in HFD-fed mice Cell metabolism High 33571454
2021 GIPR agonism improves insulin sensitivity in obese mice in a weight-independent manner by enhancing glucose disposal in white adipose tissue (WAT). This effect is associated with reduced circulating branched-chain amino acids (BCAAs) and ketoacids, and upregulation of catabolism genes in brown adipose tissue. The effect is demonstrable in Glp-1r-null mice, confirming GLP-1R independence. Tirzepatide and long-acting GIPR agonist (LAGIPRA) treatment in obese WT and Glp-1r-null mice; hyperinsulinemic-euglycemic clamp; WAT glucose disposal measurement; plasma BCAA measurement; RNA sequencing of adipose tissue The Journal of clinical investigation High 34003802
2021 GIPR is predominantly expressed in pericytes and mesothelial cells rather than adipocytes within white adipose tissue (WAT), as determined by single-nucleus RNA-sequencing and genetic lineage-targeting experiments showing that adiponectin-Cre does not reduce WAT Gipr expression, whereas nonadipocyte-selective Cre drivers markedly reduce it. Single-nucleus RNA-sequencing; Adipoq-Cre:Giprflx/flx, Ap2/Fabp4-Cre, Ubc-Cre, adenoviral CMV-Cre mouse models; WAT Gipr expression quantification Diabetes High 35192688
2021 Simultaneous GIPR blocking and GLP-1R activation by bispecific GIPR-Ab/GLP-1 molecules leads to rapid receptor internalization and amplified endosomal cAMP production in cells co-expressing both receptors, providing a mechanistic basis for their superior efficacy. Cell-based cAMP assay in recombinant cells co-expressing GIPR and GLP-1R; receptor internalization imaging Cell reports. Medicine Medium 34095876
2021 GIPR in GABAergic neurons is required for the anti-aversive (anti-nausea) effect of GIPR agonism and the enhanced weight loss achieved by dual incretin agonism. Global or GABAergic neuron-specific GIPR KO protects against diet-induced obesity, whereas glutamatergic GIPR KO has negligible effect. GABAergic neuron-specific and glutamatergic neuron-specific Gipr KO mice; conditioned taste aversion assay; dual agonist treatment; body weight/food intake measurement Diabetes High 35499381
2021 GIPR signaling in myeloid immune cells supports type 2 immune responses in visceral white adipose tissue (epiWAT) during obesity. Loss of GIPR in myeloid cells reduces group 2 innate lymphoid cells, eosinophils, and Tregs in epiWAT; S100A8/A9 alarmin mediates this suppression, as co-deletion of S100A9 rescues type 2 cytokine expression. Bone marrow chimerism (Gipr-/- BM transplant); LysM-Cre myeloid-specific GIPR KO; flow cytometry; cytokine expression analysis; S100a9/Gipr double KO Frontiers in immunology Medium 33717200
2020 GIPR signaling in bone marrow controls expression of Toll-like receptor (TLR) and Notch-related genes regulating hematopoiesis. Loss of BM GIPR attenuates adipose tissue inflammation and dysregulates hematopoietic response to bone marrow transplantation, though the magnitude of cellular changes in hematopoiesis is relatively modest. Global Gipr-/- and GiprTie2-/- mice; bone marrow transplantation; pharmacological GIPR agonism; hematopoietic stressors (5-FU, LPS, Pam3CSK4); gene expression analysis Molecular metabolism Medium 32389828
2021 GIPR structural interaction studies using homology modeling and in vitro mutational analysis identified residues R183(2.60), R190(2.67), and R300(5.40) as key for receptor activation, and a K293ECL2–E362ECL3 salt bridge whose disruption by antagonists strongly reduces GIPR activation. GIP(1-30)NH2 and GIP(1-42) show different binding modes from antagonists GIP(3-30)NH2 and GIP(5-30)NH2. Homology modeling based on GLP-1R structure; molecular dynamics simulations; in vitro site-directed mutagenesis and functional assay Structure Medium 33891864
2022 Peripheral GIPR agonism activates neurons in the area postrema (AP) and reduces PYY-induced neuronal activity in the parabrachial nucleus (PBN), explaining the anti-nausea effect. Gipr and Npy2r are co-expressed in AP neurons, providing a substrate for GIP-PYY interaction at the brainstem level. Central/peripheral GIPR agonist administration; conditioned taste avoidance assay; whole-brain cFos immunohistochemistry; in situ hybridization for Gipr and Npy2r co-expression Diabetes Medium 35499381
2022 GIPR loss in Apoe-/- mice increases aortic atherosclerosis and aortic/hepatic inflammation despite reduced body weight, demonstrating a GIPR-dependent anti-inflammatory/anti-atherosclerotic function. Bone marrow transplantation experiments did not implicate BM-derived GIPR+ cells as the primary mediator. Apoe-/-:Gipr-/- double KO mice; AAV-PCSK9 atherosclerosis model; bone marrow transplantation; aortic plaque quantification; gene expression analysis Molecular metabolism Medium 36055579
2023 In human islets (but not mouse islets), antagonizing GIPR consistently decreases the insulin, glucagon, and somatostatin secretory response to tirzepatide, demonstrating that tirzepatide acts through both incretin receptors in human islets. In mouse islets, tirzepatide acts predominantly through GLP-1R due to reduced potency at mouse GIPR. Human and mouse islet perifusion; selective GIPR antagonist co-treatment; insulin/glucagon/somatostatin secretion measurement Nature metabolism High 37277609
2023 Prolonged GLP-1R activation leads to endosomal cAMP signaling and receptor degradation, whereas GIPR shows preferentially plasma membrane recycling, reduced desensitization, and enhanced downstream signal amplification in pancreatic beta cells. GIPR has increased plasma membrane recycling and lower internalization compared to GLP-1R. Surface expression measurement; receptor trafficking imaging; cAMP signaling assays at plasma membrane vs endosomes; internalization/degradation assays in pancreatic beta cells Endocrinology Medium 36774542
2023 Mass spectrometry identified eight serine phosphorylation sites on GIPR—one in an intracellular loop and the rest in the C-terminal domain. GIP stimulation enhances phosphorylation at four sites, and tirzepatide enhances the same four plus a unique fifth site, revealing a pharmacologically distinct phosphorylation signature for the synthetic dual agonist. TIMS-TOF mass spectrometry; GIP and tirzepatide stimulation; phosphosite mapping Journal of the American Chemical Society High 38091482
2023 Two N-terminus-altered splice variants of GIPR (SV1/GIPR-202 and SV2/GIPR-209) neither bind GIP nor signal independently but suppress ligand binding and cAMP accumulation of full-length GIPR when co-expressed. Cryo-EM structures show these SVs occupy the ligand-binding pocket via inward-folded TM1/6/7 and ECL2/3, providing a ligand-independent dominant-negative mechanism. Cryo-EM structure determination; HEK293T co-expression; cAMP assay; β-arrestin recruitment assay; cell surface localization Proceedings of the National Academy of Sciences of the United States of America High 37792509
2024 Cryo-EM structures of ligand-free GIPR in complex with Gs protein show that Gs alone directly opens the intracellular binding cavity and rearranges the extracellular pocket, with the TM6-ECL3 juncture of GIPR partially occupying the peptide-binding site—a conformation distinct from the peptide-bound active state and representing a transitional Gs-stabilized state. Cryo-EM structure determination of ligand-free GIPR-Gs complex; structural comparison with peptide-bound structures Cell discovery High 38346960
2024 β-arrestin 2 recruitment is required for full GIPR biological activity. GIPR variants impaired in both Gs signaling and β-arrestin 2 recruitment show greater association with reduced adiposity-related traits than variants impaired in Gs alone. Genetic ablation of β-arrestin 2 in mice impairs GIP-stimulated cAMP production and reduces GIP efficacy on glucose control. Endosomal Gs-mediated GIPR signaling shows β-arrestin dependency. In vitro pharmacological characterization of 47 GIPR variants (Gs/cAMP, β-arrestin 2, internalization assays); human burden testing; β-arrestin 2 KO mice; glucose tolerance testing Nature metabolism High 38871982
2024 The GIPR Q354 variant (rs1800437) causes enhanced intracellular dwell time and increased localization to the Trans-Golgi Network after agonist stimulation in beta cells, altering spatiotemporal signaling without affecting cAMP generation per se. This altered trafficking is associated with increased GIP sensitivity in vivo and resistance to diet-induced obesity in mice. CRISPR-Cas9 knock-in mouse model (GIPR-Q350); ex vivo islet insulin secretion; in vivo glucose tolerance; receptor trafficking imaging in beta cell line Molecular metabolism Medium 37925022
2024 GIPR agonism enhances the insulin-sensitizing effect of the TZD rosiglitazone and prevents rosiglitazone-induced weight gain in obese insulin-resistant mice, with systemic insulin sensitization associated with increased glucose disposal in brown adipose tissue and upregulation of metabolic/thermogenic genes. Rosiglitazone itself induces GIPR mRNA expression in white and brown fat. Long-acting GIPR agonist + rosiglitazone co-treatment in obese GIPR-null and WT mice; insulin tolerance testing; BAT gene expression by RNA sequencing; body weight/food intake measurement Diabetes Medium 37934926
2024 GIPR signaling in GABAergic neurons is essential for the enhanced weight loss of dual GLP-1R/GIPR agonism and for the anti-aversive effect of GIPR agonism. GABAergic neuron-specific GIPR KO enhances the weight loss efficacy of GLP-1R agonism alone, while loss of GIPR in glutamatergic neurons has negligible effect. GABAergic- and glutamatergic-neuron-specific Gipr KO mice; dual agonist and single-agonist drug treatment; body weight, food intake, conditioned taste aversion measurements Molecular metabolism High 39612941
2024 Loss of GIPR in leptin receptor-expressing (Lepr+) cells impairs the superior glycemic effect of GIPR:GLP-1R co-agonism over single GLP-1R agonism, without affecting body weight or food intake, consistent with the high co-localization of Gipr and Lepr in pancreatic beta cells. Lepr-Cre:Giprflx/flx mice; acyl-GIP and MAR709 treatment; glucose tolerance testing; single-cell RNA-seq of hypothalamus, hindbrain, and pancreas; body weight/food intake measurement Molecular metabolism Medium 38492844
2025 GIPR agonism and antagonism reduce body weight via distinct mechanisms: GIPR agonism requires GABAergic GIPR+ neurons and is GLP-1R-independent, whereas GIPR antagonism requires functional GLP-1R signaling and is eliminated in Glp-1r KO mice but preserved in GABAergic or peripheral neuron-specific Gipr KO mice. Single-nucleus RNA-seq shows opposing gene expression effects of agonism vs. antagonism in the dorsal vagal complex. Global Gipr-/-, global Glp1r-/-, GABAergic-specific, and PNS-specific Gipr KO mice; GIPR agonist/antagonist treatment; body weight and food intake; single-nucleus RNA-seq of dorsal vagal complex Nature metabolism High 40301583
2025 Chronic GIPR agonism produces homologous functional GIPR desensitization in isolated pancreatic islets (reduced cAMP re-challenge response) and in vivo (reduced anti-hyperglycemic response to GIP re-challenge), despite therapeutic weight loss and improved glucose homeostasis. GIPR shows minimal agonist-induced internalization or β-arrestin 2 activation, suggesting desensitization occurs through a distinct mechanism. Live-cell cAMP imaging in dispersed pancreatic islets; receptor internalization and β-arrestin 2 assays in vitro; in vivo glucose tolerance testing after GIP108 pre-treatment in mice Molecular metabolism Medium 39788289
2012 Resistin regulates GIPR expression in adipocytes via c-Jun-mediated transcriptional activation through a TPA-response element (TRE-III) in the Gipr promoter. Loss of resistin in Retn-/- mice greatly reduces adipocyte GIPR expression, abrogating GIP-stimulated PKB/LKB1/AMPK/LPL pathway activity and fatty acid uptake. Primary adipocytes from Retn-/-, Retn+/-, Retn+/+ mice; GIP stimulation assays; chromatin immunoprecipitation; GIPR mRNA/protein quantification; LPL activity assay Diabetes Medium 23002036
2014 GIP promotes interaction of GRK2 with GIPR (by immunoprecipitation) and decreases association of GRK2 with IRS-1 in human adipocytes, functioning as an insulin sensitizer by enhancing insulin signaling. This GIP-mediated sensitization is absent under hypoxia or in adipocytes from obese patients with reduced GIPR expression. Co-immunoprecipitation of GRK2-GIPR and GRK2-IRS1; glucose uptake assays; insulin signaling analysis in human adipocyte cell lines under normoxia/hypoxia and in lean vs obese adipose-derived stem cells The Journal of clinical endocrinology and metabolism Medium 24512489
2025 GIPR activation in somatotroph GH3 cells stably expressing human GIPR induces cAMP/PKA and MAPK/ERK signaling, enhances GH and prolactin secretion, and increases intracellular calcium oscillations dependent on extracellular calcium influx, without affecting cell proliferation or viability. Stable GIPR-overexpressing GH3 cell line; cAMP/PKA assay; ERK activation; GH/prolactin secretion measurement; calcium imaging; cell viability assay; transcriptomics Endocrine-related cancer Medium 41066443
2009 GIPR is expressed in peripheral nervous system neurons (DRG), myelinating Schwann cells, satellite cells, oligodendrocytes, and ependymal cells. In Schwann cells, GIPR shows polarized localization to abaxonal membranes. GIPR-deficient mice exhibit impaired axonal regeneration after sciatic nerve crush, establishing a role for GIP/GIPR signaling in nerve regeneration. Immunohistochemistry; quantitative RT-PCR after sciatic nerve crush; in vivo analysis of Gipr-/- mice after nerve crush injury Journal of neuroscience research Medium 19170165
2022 GIPR activation in the anterior cingulate cortex (ACC) produces analgesic and anxiolytic effects in a chronic inflammatory pain model, acting by inhibiting neuroinflammation, reducing microglial activation, reversing upregulation of NMDA and AMPA receptors, and suppressing excitatory neurotransmission. These effects are blocked by GIPR antagonist and GIPR shRNA knockdown in the ACC. CFA chronic pain mouse model; intraperitoneal and ACC microinjection of GIPR agonist/antagonist; GIPR shRNA knockdown in ACC; von Frey/radiant heat testing; whole-cell patch-clamp; Western blot; immunofluorescence Frontiers in endocrinology Medium 35712239
2025 GIPR agonism and antagonism have distinct metabolic profiles in lean and obese mice: GIPR agonism improves glucose tolerance independently of weight loss, whereas GIPR antagonism reduces insulin sensitivity compared to pair-fed controls. Neither treatment affects energy expenditure; weight loss matches pair-fed controls. GIPR antagonism reduces adipose tissue lipolytic gene expression. GIP108 agonist and NN-GIPR-Ant antagonist treatment in lean/obese mice; pair-feeding; glucose and insulin tolerance tests; liver triglyceride measurement; adipose tissue gene expression Diabetes, obesity & metabolism Medium 41287212

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2021 The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling. Cell metabolism 256 33571454
2018 Anti-obesity effects of GIPR antagonists alone and in combination with GLP-1R agonists in preclinical models. Science translational medicine 195 30567927
2018 Optimized GIP analogs promote body weight lowering in mice through GIPR agonism not antagonism. Molecular metabolism 195 30578168
2021 GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese mice. The Journal of clinical investigation 193 34003802
2024 A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings. Nature metabolism 152 38316982
2020 Chronic glucose-dependent insulinotropic polypeptide receptor (GIPR) agonism desensitizes adipocyte GIPR activity mimicking functional GIPR antagonism. Nature communications 126 33020469
2015 TCF1 links GIPR signaling to the control of beta cell function and survival. Nature medicine 126 26642437
2023 GIPR/GLP-1R dual agonist therapies for diabetes and weight loss-chemistry, physiology, and clinical applications. Cell metabolism 106 37591245
2023 The incretin co-agonist tirzepatide requires GIPR for hormone secretion from human islets. Nature metabolism 96 37277609
2014 Disruption of GIP/GIPR axis in human adipose tissue is linked to obesity and insulin resistance. The Journal of clinical endocrinology and metabolism 93 24512489
2014 A functional amino acid substitution in the glucose-dependent insulinotropic polypeptide receptor (GIPR) gene is associated with lower bone mineral density and increased fracture risk. The Journal of clinical endocrinology and metabolism 82 24446656
2021 GIPR antagonist antibodies conjugated to GLP-1 peptide are bispecific molecules that decrease weight in obese mice and monkeys. Cell reports. Medicine 78 34095876
1995 Human gastric inhibitory polypeptide receptor: cloning of the gene (GIPR) and cDNA. Genomics 73 8575774
2022 GIPR Is Predominantly Localized to Nonadipocyte Cell Types Within White Adipose Tissue. Diabetes 56 35192688
2022 GIPR Agonism Inhibits PYY-Induced Nausea-Like Behavior. Diabetes 55 35499381
2016 Use of CRISPR/Cas9-engineered INS-1 pancreatic β cells to define the pharmacology of dual GIPR/GLP-1R agonists. The Biochemical journal 47 27422784
2022 Discovery of a potent GIPR peptide antagonist that is effective in rodent and human systems. Molecular metabolism 42 36400403
2017 Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing's syndrome. JCI insight 42 28931750
2024 Characterization of genetic variants of GIPR reveals a contribution of β-arrestin to metabolic phenotypes. Nature metabolism 41 38871982
2009 Glucose-dependent insulinotropic polypeptide (GIP) and its receptor (GIPR): cellular localization, lesion-affected expression, and impaired regenerative axonal growth. Journal of neuroscience research 41 19170165
2021 GIPR Function in the Central Nervous System: Implications and Novel Perspectives for GIP-Based Therapies in Treating Metabolic Disorders. Diabetes 39 34176786
2017 The GIP/GIPR axis is functionally linked to GH-secretion increase in a significant proportion of gsp- somatotropinomas. European journal of endocrinology 39 28179449
2016 Novel GLP-1R/GIPR co-agonist "twincretin" is neuroprotective in cell and rodent models of mild traumatic brain injury. Experimental neurology 39 27845037
2011 Gipr is essential for adrenocortical steroidogenesis; however, corticosterone deficiency does not mediate the favorable metabolic phenotype of Gipr(-/-) mice. Diabetes 38 22043004
2022 GIP and GLP-2 together improve bone turnover in humans supporting GIPR-GLP-2R co-agonists as future osteoporosis treatment. Pharmacological research 37 34995796
2021 Reagents and models for detecting endogenous GLP1R and GIPR. EBioMedicine 37 34911028
2022 Designing a Dual GLP-1R/GIPR Agonist from Tirzepatide: Comparing Residues Between Tirzepatide, GLP-1, and GIP. Drug design, development and therapy 36 35651477
2023 Enhanced Endosomal Signaling and Desensitization of GLP-1R vs GIPR in Pancreatic Beta Cells. Endocrinology 35 36774542
2007 Association analyses of GIP and GIPR polymorphisms with traits of the metabolic syndrome. Molecular nutrition & food research 34 17624916
2011 Postnatal development of numbers and mean sizes of pancreatic islets and beta-cells in healthy mice and GIPR(dn) transgenic diabetic mice. PloS one 33 21818396
2020 The gut hormone receptor GIPR links energy availability to the control of hematopoiesis. Molecular metabolism 31 32389828
2025 GIPR agonism and antagonism decrease body weight and food intake via different mechanisms in male mice. Nature metabolism 30 40301583
2013 Gastric inhibitory polypeptide receptor (GIPR) is a promising target for imaging and therapy in neuroendocrine tumors. Surgery 30 24238043
2024 Immunomodulation and inflammation: Role of GLP-1R and GIPR expressing cells within the gut. Peptides 26 38555054
2024 AT-7687, a novel GIPR peptide antagonist, combined with a GLP-1 agonist, leads to enhanced weight loss and metabolic improvements in cynomolgus monkeys. Molecular metabolism 24 39128651
2020 The pathogenic role of the GIP/GIPR axis in human endocrine tumors: emerging clinical mechanisms beyond diabetes. Reviews in endocrine & metabolic disorders 24 31933128
2024 Specific loss of GIPR signaling in GABAergic neurons enhances GLP-1R agonist-induced body weight loss. Molecular metabolism 23 39612941
2022 Genetic disruption of the Gipr in Apoe-/- mice promotes atherosclerosis. Molecular metabolism 23 36055579
2024 GLP1R and GIPR expression and signaling in pancreatic alpha cells, beta cells and delta cells. Peptides 22 38360354
2024 Molecular features of the ligand-free GLP-1R, GCGR and GIPR in complex with Gs proteins. Cell discovery 21 38346960
2021 Investigating GIPR (ant)agonism: A structural analysis of GIP and its receptor. Structure (London, England : 1993) 21 33891864
2025 GIPR-Ab/GLP-1 peptide-antibody conjugate requires brain GIPR and GLP-1R for additive weight loss in obese mice. Nature metabolism 20 40301582
2014 GIPR expression in gastric and duodenal neuroendocrine tumors. The Journal of surgical research 19 24565507
2022 The GIP/GIPR axis in medullary thyroid cancer: clinical and molecular findings. Endocrine-related cancer 17 35298396
2008 Daily administration of the GIP-R antagonist (Pro3)GIP in streptozotocin-induced diabetes suggests that insulin-dependent mechanisms are critical to anti-obesity-diabetes actions of (Pro3)GIP. Diabetes, obesity & metabolism 17 18333892
2020 GIP-GIPR promotes neurite outgrowth of cortical neurons in Akt dependent manner. Biochemical and biophysical research communications 16 33321289
2025 Biased agonism of GLP-1R and GIPR enhances glucose lowering and weight loss, with dual GLP-1R/GIPR biased agonism yielding greater efficacy. Cell reports. Medicine 15 40460831
2021 211At-Labeled Polymer Nanoparticles for Targeted Radionuclide Therapy of Glucose-Dependent Insulinotropic Polypeptide Receptor (GIPR)-Overexpressed Cancer. Bioconjugate chemistry 15 34260853
2025 Chronic GIPR agonism results in pancreatic islet GIPR functional desensitisation. Molecular metabolism 14 39788289
2024 GIPR Agonism Enhances TZD-Induced Insulin Sensitivity in Obese IR Mice. Diabetes 14 37934926
2024 Obesity Variants in the GIPR Gene Are not Associated With Risk of Fracture or Bone Mineral Density. The Journal of clinical endocrinology and metabolism 14 38118020
2021 GIPR Signaling in Immune Cells Maintains Metabolically Beneficial Type 2 Immune Responses in the White Fat From Obese Mice. Frontiers in immunology 14 33717200
2021 Distinct Identity of GLP-1R, GLP-2R, and GIPR Expressing Cells and Signaling Circuits Within the Gastrointestinal Tract. Frontiers in cell and developmental biology 14 34660576
2012 Resistin knockout mice exhibit impaired adipocyte glucose-dependent insulinotropic polypeptide receptor (GIPR) expression. Diabetes 13 23002036
2024 Regulation of energy metabolism through central GIPR signaling. Peptides 11 38527521
2022 Activation of GIPR Exerts Analgesic and Anxiolytic-Like Effects in the Anterior Cingulate Cortex of Mice. Frontiers in endocrinology 11 35712239
2015 Glucose-dependent insulinotropic polypeptide (GIP) and GIP receptor (GIPR) genes: An association analysis of polymorphisms and bone in young and elderly women. Bone reports 11 28326339
2024 Loss of GIPR in LEPR cells impairs glucose control by GIP and GIP:GLP-1 co-agonism without affecting body weight and food intake in mice. Molecular metabolism 10 38492844
2011 Association between the GIPR gene and the insulin level after glucose loading in schizophrenia patients treated with olanzapine. The pharmacogenomics journal 10 21747410
2025 Genome-wide interaction study with body mass index identifies CYP7A1 and GIPR as genetic modulators of metabolic dysfunction-associated steatotic liver disease. Clinical and molecular hepatology 9 40452229
2023 Phosphorylation Sites of the Gastric Inhibitory Polypeptide Receptor (GIPR) Revealed by Trapped-Ion-Mobility Spectrometry Coupled to Time-of-Flight Mass Spectrometry (TIMS-TOF MS). Journal of the American Chemical Society 9 38091482
2023 Safflower yellow and its main component hydroxysafflor yellow A alleviate hyperleptinemia in diet-induced obesity mice through a dual inhibition of the GIP-GIPR signaling axis. Phytotherapy research : PTR 8 36943416
2015 GIPR Gene Polymorphism and Weight Gain in Patients With Schizophrenia Treated With Olanzapine. The Journal of neuropsychiatry and clinical neurosciences 8 25321336
2025 Genetically modeled GLP1R and GIPR agonism reduce binge drinking and alcohol-associated phenotypes: a multi-ancestry drug-target Mendelian randomization study. Molecular psychiatry 7 40931165
2023 Design of novel therapeutics targeting the glucose-dependent insulinotropic polypeptide receptor (GIPR) to aid weight loss. Expert opinion on drug discovery 7 37154171
2023 Spatiotemporal regulation of GIPR signaling impacts glucose homeostasis as revealed in studies of a common GIPR variant. Molecular metabolism 7 37925022
2022 Design of Potent and Proteolytically Stable Biaryl-Stapled GLP-1R/GIPR Peptide Dual Agonists. ACS chemical biology 7 35417146
2019 Predictive effect of GIPR SNP rs10423928 on glucose metabolism liver fat and adiposity in prediabetic and diabetic subjects. Peptides 7 31874232
2025 The role of GIPR in food intake control. Frontiers in endocrinology 6 40166681
2025 Fluorescent GLP1R/GIPR dual agonist probes reveal cell targets in the pancreas and brain. Nature metabolism 6 40830598
2025 Strategic Design of Triple GLP-1R/GCGR/GIPR Agonists with Varied Receptor Potency: Achieving Comparable Glycemic and Weight Reduction Effects. Journal of medicinal chemistry 6 40958513
2023 Association of gastric inhibitory polypeptide receptor (GIPR) gene polymorphism with type 2 diabetes mellitus in iranian patients. BMC medical genomics 6 36882778
2023 Genetically proxied impaired GIPR signaling and risk of 6 cancers. iScience 6 37250804
2023 The Methylation Analysis of the Glucose-Dependent Insulinotropic Polypeptide Receptor (GIPR) Locus in GH-Secreting Pituitary Adenomas. International journal of molecular sciences 6 37298217
2010 Mapping interactions of gastric inhibitory polypeptide with GIPR N-terminus using NMR and molecular dynamics simulations. Journal of peptide science : an official publication of the European Peptide Society 6 20607844
2023 GIPR expression is induced by thiazolidinediones in a PPARγ-independent manner and repressed by obesogenic stimuli. European journal of cell biology 4 37130450
2022 Molecular Characterization of Grass Carp GIPR and Effect of Nutrition States, Insulin, and Glucagon on Its Expression. Aquaculture nutrition 4 36860432
2025 The other side of the incretin story: GIPR signaling in energy homeostasis. Cell metabolism 3 39778517
2024 Evaluating the efficacy of GIPR agonists on non-alcoholic fatty liver disease: A Mediation Mendelian Randomization Study. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 3 38735797
2022 GIPR rs10423928 and bone mineral density in postmenopausal women in Shanghai. Endocrine connections 3 35029542
2022 The Link between Three Single Nucleotide Variants of the GIPR Gene and Metabolic Health. Genes 3 36140702
2021 Chronic treatment with anti-GIPR mAb alone and combined with DPP-4 inhibitor correct obesity, dyslipidemia and nephropathy in rodent animals. Life sciences 3 33453239
2018 [The role of single nucleotide polymorphisms in GIPR gene in the changes of secretion in hormones and adipokines in patients with obesity with type 2 diabetes]. Biomeditsinskaia khimiia 3 29723152
2009 Analysis of glucose-dependent insulinotropic peptide receptor (GIPR) and luteinizing hormone receptor (LHCGR) expression in human adrenocortical hyperplasia. Arquivos brasileiros de endocrinologia e metabologia 3 19578593
2026 GLP-1R-GIPR-PPARα/γ/δ quintuple agonism corrects obesity and diabetes in mice. Nature 2 42056522
2025 Understanding the activation mechanism of GLP-1R/GIPR by dual agonist Tirzepatide via molecular dynamics and protein-peptide binding. International journal of biological macromolecules 2 40692063
2025 Binding kinetics, bias, receptor internalization and effects on insulin secretion in vitro and in vivo of a novel GLP-1R/GIPR dual agonist, HISHS-2001. Diabetes, obesity & metabolism 2 40831316
2025 GIPR in GH-PitNETs: molecular and functional insights. Endocrine-related cancer 2 41066443
2024 Gastric Inhibitory Polypeptide Receptor (GIPR) Overexpression Reduces the Tumorigenic Potential of Retinoblastoma Cells. Cancers 2 38730608
2023 Molecular basis of signal transduction mediated by the human GIPR splice variants. Proceedings of the National Academy of Sciences of the United States of America 2 37792509
2025 Binding Kinetics, Bias, Receptor Internalization and Effects on Insulin Secretion in vitro and in vivo of a Novel GLP-1R/GIPR Dual Agonist, HISHS-2001. bioRxiv : the preprint server for biology 1 39868265
2025 Design of potent and proteolytically stable double biaryl-stapled GLP-1R/GIPR peptide dual agonists. Bioorganic & medicinal chemistry 1 40311601
2025 Decoding the impact of glucose-dependent insulinotropic polypeptide receptor (GIPR) agonist on cardiometabolic health: inflammatory mediators at the focus. Diabetology & metabolic syndrome 1 40426228
2025 The Premise of the Paradox: Examining the Evidence That Motivated GIPR Agonist and Antagonist Drug Development Programs. Journal of clinical medicine 1 40507574
2025 Evaluating causal protective effect of dual GLP-1R/GIPR agonists on MASLD: A Mendelian randomization and colocalization study. European journal of pharmacology 1 40865863
2025 A metabolic comparison of GIPR agonism versus GIPR antagonism in male mice. Diabetes, obesity & metabolism 1 41287212
2025 Long-acting GIPR agonist LY3537021 reduces body weight and fasting blood glucose in patients with T2D: Preclinical development and phase 1 randomized ascending dose studies. Molecular metabolism 1 41391569
2024 An imbalanced GLP-1R/GIPR co-agonist peptide with a site-specific N-terminal PEGylation to maximize metabolic benefits. iScience 1 38510128
2020 Sexually dimorphic metabolic responses to exposure of a high fat diet during pregnancy, lactation and early adulthood in Gipr-/- mice. Peptides 1 31917165
1996 [Gastric inhibitory polypeptide (GIP) and GIP receptor (GIPR)]. Nihon rinsho. Japanese journal of clinical medicine 1 8920677

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