UniProt-P48546 — Gastric Inhibitory Polypeptide Receptor (GIPR)

[DRAFT — authored 2026-04-19. UniProt entry web-verified via REST flat-file 2026-04-19.]

Entry

UniProt accession: P48546 (entry name GIPR_HUMAN)
Alt accessions: B7WP14, B7ZKQ0, Q14401, Q16400, Q52M04, Q9UPI1
Protein name: Gastric inhibitory polypeptide receptor (GIP-R); also Glucose-dependent insulinotropic polypeptide receptor
Gene: GIPR
Organism: Homo sapiens (Human)
Sequence length: 466 amino acids
Receptor class: G-protein-coupled receptor, class B (secretin-family)

Function Summary

GIPR is the receptor for gastric inhibitory polypeptide (GIP, a.k.a. glucose-dependent insulinotropic polypeptide), released from duodenal/jejunal K-cells after nutrient ingestion. Ligand binding activates Gs-coupled adenylyl cyclase and cAMP signaling. Key actions:

Pancreatic β-cell: glucose-dependent insulin secretion potentiation (additive to GLP-1)
Adipose tissue: direct effects on lipid storage, adipocyte differentiation, and insulin-sensitizing signaling
Stomach / CNS: modulatory effects on gastric emptying and satiety, though less dominant than GLP-1
Bone: anabolic effects on osteoblasts (GIPR is expressed on bone cells)

Forms homodimers and heterodimers with GLP1R (P43220). N-glycosylation is essential for proper cell-surface localization and stability. Multiple natural splice variants exist.

Relevance to Module 5 Peptides

Tirzepatide: GIP-R arm of dual GIP/GLP-1 agonism; believed to contribute to superior weight-loss effect vs GLP-1 monoagonists via adipose insulin-sensitization and possible CNS effects
Retatrutide: GIP-R arm of triple GIP/GLP-1/glucagon agonism
CagriSema: no GIP-R component — CagriSema is amylin + GLP-1 only (contrast for teaching)

Cross-References to Vault Research Notes

PMID-35658024 – SURMOUNT-1 Tirzepatide for Obesity — SURMOUNT-1 (GIP/GLP-1 dual activation)
PMID-37385280 – Retatrutide Phase 2 Trial in Type 2 Diabetes — retatrutide T2D
PMID-38856224 – Sanyal Tirzepatide MASH Phase 2 SYNERGY-NASH — tirzepatide MASH
UniProt-P43220 – GLP1R GLP-1 Receptor — heterodimer partner

Orchestrator Notes

Primary mechanism reference for Tirzepatide and Retatrutide profile Mechanism sections.
Verified 2026-04-19 via UniProt REST flat-file API (https://rest.uniprot.org/uniprotkb/P48546.txt).