Amylin (mouse/rat): safer rodent form of the meal-time blood-sugar hormone
The mouse and rat version of amylin, a hormone released with insulin after eating that slows digestion and reduces appetite; used in lab research and as the template for pramlintide, an FDA-approved diabetes drug.
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
Amylin (mouse, rat) is the rodent form of a 37-amino-acid hormone that pancreatic beta cells co-secrete with insulin after a meal. In rats and mice the peptide carries six amino-acid substitutions relative to human amylin (most consequentially at positions 25, 28, and 29) that prevent it from clumping into the toxic fibrils its human counterpart forms — and that prevention is exactly why this rodent sequence has been studied for decades as a non-amyloidogenic reference peptide and as the structural template for the only FDA-approved amylin drug, pramlintide. The mature peptide carries a C-terminal amide and an intramolecular disulfide bond between Cys2 and Cys7; neither modification is visible in the raw 37-letter sequence shown on this card.
History
Amylin was identified in the mid-1980s as the principal protein constituent of islet amyloid deposits seen in pancreases of people with type-2 diabetes — a finding that linked a then-unknown peptide to a long-puzzling histological feature of the disease (Leffert and colleagues, PNAS, 1989). The rat amylin cDNA was cloned shortly afterward, showing that the peptide is generated by proteolytic processing of a 93-amino-acid precursor expressed selectively in pancreatic islets and bordered by dibasic cleavage sites in a pattern resembling that of calcitonin gene-related peptide (Leffert and colleagues, PNAS, 1989). Recognition that the rat sequence resisted amyloid formation while retaining biological activity made it the design starting point for pramlintide, in which the proline-containing residues at positions 25, 28, and 29 of rat amylin were grafted into the human backbone to yield a soluble, non-aggregating analog that the FDA approved in 2005 (Hoogwerf and colleagues, Drug Design, Development and Therapy, 2008).
What it does
In vivo, amylin acts as a satiety and glucose-regulatory hormone: it slows gastric emptying, suppresses glucagon release, and signals meal-related satiety to the brainstem. Its rodent form is widely used in preclinical pharmacology because it produces these effects without the cytotoxic aggregation that complicates work with human amylin. The peptide engages a family of receptors built from the calcitonin receptor (CALCR) in complex with one of three receptor activity-modifying proteins (RAMP1, RAMP2, or RAMP3), generating the AMY1, AMY2, and AMY3 receptor subtypes — high-affinity amylin receptors that do not exist without the RAMP partner (Hay and colleagues, Pharmacological Reviews, 2015; Poyner and colleagues, Pharmacological Reviews, 2002). Although amylin receptors share the calcitonin receptor core with calcitonin signaling, amylin's primary physiological role is metabolic rather than skeletal.
Mechanism
The amylin receptor complex couples primarily to Gαs, raising intracellular cAMP, with Gq-mediated ERK1/2 phosphorylation and Ca²⁺ mobilization as secondary signaling outputs (Hay and colleagues, Pharmacological Reviews, 2015). The six rodent-specific substitutions that distinguish this peptide from human amylin — at positions 18, 23, 25, 26, 28, and 29 — cluster in the central "amyloidogenic core" region (residues roughly 18–29); proline substitutions at 25, 28, and 29 in particular act as helix- and β-sheet-breaking residues that prevent the conformational transitions required for fibril nucleation, which is why rodents do not develop islet amyloid even though they express amylin at physiological concentrations (Cao and colleagues, FEBS Letters, 2013). Reversing those substitutions one at a time in rat amylin (for example R18H, L23F, or V26I) is sufficient to restore fibril-forming competence, identifying the central region as the molecular switch for amyloidogenicity (Green and colleagues, Journal of Molecular Biology, 2003).
Evidence
- Human: No clinical trials of native rodent amylin in humans. The rat-amylin-derived analog pramlintide is FDA-approved as adjunctive therapy with insulin for type 1 and type 2 diabetes (Hoogwerf and colleagues, Drug Design, Development and Therapy, 2008).
- Animal: Foundational work characterizing tissue-specific amylin expression and precursor processing in rat pancreatic islets established the peptide as a beta-cell co-secretion product (Leffert and colleagues, PNAS, 1989). Subsequent studies showed rat amylin influences endocrine but not exocrine pancreatic function in vivo.
- In vitro: Under standard physiological buffers rat amylin does not form amyloid fibrils and is non-cytotoxic, in direct contrast to the human sequence; under non-physiological conditions (e.g., Tris-HCl buffer with extended incubation) it can be coaxed into fibril formation, and the resulting fibrils show cytotoxicity to pancreatic and neuronal cells that is blocked by the amylin-receptor antagonist AC187 (Milton and Harris, Micron, 2013).
Known effects
- Satiety and gastric-emptying signaling — Established mechanism in rodent and human studies (pramlintide as the clinical translation).
- Glucagon suppression — Established mechanism; basis for pramlintide's postprandial glucose-control indication.
- Non-amyloidogenic reference peptide — Widely used in vitro control for studies of human amylin aggregation and IAPP-related cytotoxicity.
Regulatory status
- US: This rodent sequence is a research reagent, not a therapeutic. The structurally related human-sequence analog pramlintide (Symlin) was FDA-approved in March 2005 as an adjunct to insulin for type 1 and type 2 diabetes.
- EU: Native rodent amylin has no marketing authorization; pramlintide was not authorized by the EMA.
- WADA: Not on the WADA Prohibited List as a named substance.
Related peptides
- Human amylin (IAPP) — differs from rat amylin at six residues; the amyloidogenic counterpart implicated in type-2-diabetes islet amyloid.
- Pramlintide — synthetic analog combining the human amylin backbone with three proline substitutions (positions 25, 28, 29) borrowed from rat amylin to confer solubility; the only FDA-approved amylin drug.
- Cagrilintide — long-acting amylin analog under clinical development in combination with semaglutide for obesity.
- Calcitonin gene-related peptide (CGRP) — closest sequence relative; shares the calcitonin-receptor–RAMP receptor architecture.
- Calcitonin — defines the receptor (CALCR) at the core of the amylin receptor complex.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.7213800549507141 | openfold3-mlx |
| ranking score | 0.8148210644721985 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.885 | global PDE — lower = better |
| disorder | 0.194 | fraction disordered |
| chain pair ipTM (A, B) | 0.721 | 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 | 464s |
| predicted by | mlx@peptide |
| predicted at | 2026-04-24 |
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{pep10609,
sequence = {KCNTATCATQRLANFLVRSSNNLGPVLPPTNVGSNTY},
target = {calcr},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}