GIP: gut hormone that boosts insulin after meals (Gastric inhibitory polypeptide)
A natural gut hormone released after eating that tells the pancreas to release insulin; also has mild germ-killing properties. Natural hormone, not an approved drug on its own.
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
What this is
Gastric inhibitory polypeptide (GIP) is a gut hormone released from specialized cells lining the small intestine after a meal. It acts as an incretin — a hormone that amplifies the pancreas's insulin response to food — and is one of the two primary incretins in mammals, alongside GLP-1 (Seino and colleagues, 2010). The sequence stored here is the 36-residue fragment GIP(7–42), isolated from porcine (Sus scrofa) intestine by Agerberth and colleagues (1993) during a search for antibacterial peptides. In addition to its metabolic role, this fragment was found to retain antibacterial activity against Bacillus megaterium (Agerberth and colleagues, 1993). GIP has attracted renewed drug-development interest as one of the two receptor targets of tirzepatide, the dual GIP/GLP-1 receptor agonist approved for type 2 diabetes and obesity.
History
GIP was first identified in the late 1960s and early 1970s as a factor from the upper small intestine that inhibited gastric acid secretion — hence the original name "gastric inhibitory polypeptide." The fuller history of GIP from 1969 to 2000 is documented by Marks (2020), tracing its transformation from a minor enterogastrone into a recognized major metabolic hormone. The receptor (GIPR) was cloned in 1993 by Usdin and colleagues, who showed it to be a member of the secretin–vasoactive intestinal peptide receptor family and found it widely distributed in peripheral organs and the brain (Usdin and colleagues, 1993). In the same year, Agerberth and colleagues isolated GIP(7–42) from pig intestine in the course of searching for novel antibacterial peptides, discovering that this N-terminally truncated fragment retained direct antimicrobial activity against Bacillus megaterium (Agerberth and colleagues, 1993).
What it does
GIP is secreted postprandially from enteroendocrine K-cells in the duodenum and proximal jejunum. It binds the GIP receptor (GIPR), a class B G-protein-coupled receptor, and triggers an increase in cyclic AMP (cAMP) inside pancreatic β-cells, amplifying glucose-stimulated insulin secretion (Seino and colleagues, 2010). Effects extend beyond the pancreas: GIPR is expressed in adipose tissue, bone, brain, and other peripheral organs (Usdin and colleagues, 1993; Seino and colleagues, 2010). Bone metabolism studies cited in Seino and colleagues (2010) linked GIP signaling to new bone formation after meals. The GIP(7–42) fragment studied by Agerberth and colleagues additionally exerts direct antibacterial activity, a function independent of the GIPR-mediated incretin effect (Agerberth and colleagues, 1993). Pharmacological characterization of GIPR ligands has shown important species differences: (Pro3)GIP behaves as a full agonist at the human GIPR but as a partial agonist and competitive antagonist at rodent receptors, a distinction with meaningful implications for animal-model studies (Sparre-Ulrich and colleagues, 2016).
Evidence
- Human: GIPR signaling underpins the incretin component of tirzepatide, a dual GIP/GLP-1 receptor agonist approved for type 2 diabetes and obesity; Bailey and colleagues (2024) review duodenal enteroendocrine cells and GIP as treatment targets. The GIPR antagonist–GLP-1 conjugate AMG 133 (maridebart cafraglutide) demonstrated weight loss in a Phase 1 study (Véniant and colleagues, 2024).
- Animal: Antibacterial activity of GIP(7–42) was demonstrated in in vitro assays against Bacillus megaterium using material isolated from pig intestine (Agerberth and colleagues, 1993).
- In vitro: GIPR was cloned and characterized in transfected cell systems; receptor binding activates cAMP in pancreatic β-cells (Usdin and colleagues, 1993; Seino and colleagues, 2010). Species-dependent pharmacology of GIPR agonists and antagonists has been characterized in receptor-transfected cell lines (Sparre-Ulrich and colleagues, 2016).
Known effects
- Incretin / insulin secretion — Well-established; fundamental mechanism documented across decades of research (Seino and colleagues, 2010; Marks, 2020)
- Adipose tissue metabolism — GIPR expressed on adipocytes; functional role in lipid metabolism described (Seino and colleagues, 2010)
- Bone formation — GIP linked to postprandial new bone formation in animal models (cited in Seino and colleagues, 2010)
- Antibacterial activity (GIP(7–42) fragment) — Demonstrated in vitro; preclinical only (Agerberth and colleagues, 1993)
Regulatory status
- US / EU: GIP itself is not approved as a drug. It is the target (via GIPR agonism) of tirzepatide (Mounjaro/Zepbound), which is FDA- and EMA-approved. The GIPR antagonist conjugate AMG 133 (maridebart cafraglutide) was in Phase 1 as of Véniant and colleagues (2024).
- Research use: GIP(7–42) is used as a research tool peptide to probe GIPR pharmacology and the incretin axis.
Mechanism
GIP(7–42) binds the GIPR, a class B (secretin family) G-protein-coupled receptor (Usdin and colleagues, 1993). The GIPR couples to Gαs, activating adenylyl cyclase and raising intracellular cAMP in target cells — primarily pancreatic β-cells, where cAMP-dependent signaling amplifies glucose-stimulated insulin exocytosis (Seino and colleagues, 2010). The receptor is also expressed in adipose tissue, bone, brain, and peripheral organs, consistent with GIP's broader anabolic role (Usdin and colleagues, 1993). The N-terminal truncation in GIP(7–42) relative to full-length GIP(1–42) removes six residues but preserves GIPR-binding capacity; the same fragment also carries a separable antibacterial activity not dependent on GIPR engagement (Agerberth and colleagues, 1993). GIPR pharmacology shows notable interspecies variation: ligands such as (Pro3)GIP that act as full agonists at the human receptor behave as partial agonists or competitive antagonists at rodent receptors, complicating direct translation of murine GIPR studies to humans (Sparre-Ulrich and colleagues, 2016).
Related peptides
- Tirzepatide — dual GIP/GLP-1 receptor agonist approved for type 2 diabetes and obesity; GIP receptor agonism is a core component of its mechanism
- GLP-1 / GLP-1 analogs — the other primary incretin hormone; acts via GLP-1R rather than GIPR; see the GLP-1 family cards on this platform for semaglutide, liraglutide, and related analogs
- AMG 133 (maridebart cafraglutide) — investigational GIPR antagonist conjugated to GLP-1 analogs; Phase 1 weight-loss data reported by Véniant and colleagues (2024)
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.6616557836532593 | openfold3-mlx |
| ranking score | 0.745661199092865 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.812 | global PDE — lower = better |
| disorder | 0.161 | fraction disordered |
| chain pair ipTM (A, B) | 0.662 | interface quality |
▸3-letter notation
▸recipeopenfold3-mlx 0.3.1
| parameter | value |
|---|---|
| model | openfold3-mlx 0.3.1 |
| weights | aedd8f3eb814e392… |
| hardware | apple_m4_base_16gb |
| mlx version | 0.31.1 |
| python | 3.14.3 |
| random seed | 42 |
| msa strategy | colabfold |
| diffusion samples | 1 |
| runtime | 442s |
| predicted by | mlx@peptide |
| predicted at | 2026-04-22 |
python3 openfold3/run_openfold.py predict --query_json {query.json} --runner_yaml examples/example_runner_yamls/mlx_runner.yml --output_dir {output_dir} --num_diffusion_samples 1 ▸citationbibtex
@peptide{pep10606,
sequence = {ISDYSIAMDKIRQQDFVNWLLAQKGKKSDWKHNITQ},
target = {gipr},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}