Peptides›Metabolic›Amylin (native)

Amylin (native)

/ Endogenous 37-residue islet amyloid polypeptide; co-secreted with insulin from beta-cells; CTR/RAMP-amylin receptor agonist

TIER 3 · PreclinicalN = 0 · TESTING PENDINGMW 3903.00 g·mol⁻¹

ALIAS · Islet amyloid polypeptide · IAPP · Amylin (native)

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Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

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§ A · Identity

Primary sequenceKCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY-NH2

MW · 3903.00CLASS · Endogenous 37-residue islet amyloid polypeptide; co-secreted with insulin from beta-cells; CTR/RAMP-amylin receptor agonistCATEGORY · Metabolic

Tier 3 for the native peptide. Native amylin is a foundational paracrine satiety and glucose-control hormone, but the clinical translation runs through analogs - pramlintide (Symlin, FDA-approved 2005 for type 1 and type 2 diabetes adjunct to mealtime insulin) and cagrilintide (a long-acting amylin analog under investigation as a CagriSema combination with semaglutide). The native peptide itself is not approved.

§ B · Mechanism of action

Amylin is a 37-residue C-terminally amidated peptide co-secreted with insulin from pancreatic beta-cells in response to nutrient stimulation. The native peptide contains a single intramolecular disulfide bond between Cys2 and Cys7. Its receptor is a heterodimer of the calcitonin receptor (CTR) with one of three receptor activity-modifying proteins (RAMP1, RAMP2, or RAMP3), generating the AMY1, AMY2, and AMY3 receptor subtypes.

Functionally, amylin slows gastric emptying, suppresses postprandial glucagon secretion, and engages central satiety circuits at the area postrema and nucleus tractus solitarius - actions complementary to insulin in postprandial glucose control. The peptide is highly amyloidogenic in humans (residues 20-29 form the IAPP amyloid core deposited in islets in type 2 diabetes), which constrained development of the native peptide as a therapeutic and motivated the engineering of pramlintide (three proline substitutions confer non-amyloidogenicity).

Native amylin is the reference ligand whose pharmacology informs the amylin-analog drug class - pramlintide, davalintide, and the long-acting cagrilintide. CagriSema (cagrilintide plus semaglutide) is in late-stage development for obesity and type 2 diabetes.

§ C · Human clinical evidence

No development of native amylin as a therapeutic in humans because of the amyloidogenicity problem. The clinical evidence base sits with the analog class: pramlintide pivotal trials (FDA approval 2005), cagrilintide Phase 1-2 (Lau 2021), and CagriSema Phase 2/3 (REDEFINE program). Native amylin appears in human pharmacology only as an experimental probe in research settings.

§ D · Primary literature

PubMed3317417Cooper GJ et al. — Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients · Proceedings of the National Academy of Sciences USA · in-vitroOriginal isolation and partial sequencing of amylin (then 'islet amyloid polypeptide') from amyloid-rich pancreatic tissue of type 2 diabetic patients - foundational discovery establishing IAPP as a beta-cell co-secretory peptide.Limitations: Discovery / structural paper; preclinical.1987

PubMed20357016Lutz TA et al. — The role of amylin in the control of energy homeostasis · American Journal of Physiology. Regulatory, Integrative and Comparative Physiology · reviewComprehensive review of amylin's central and peripheral roles in energy homeostasis - area postrema satiety signalling, gastric emptying, glucagon suppression, and the receptor pharmacology underpinning the analog drug class.Limitations: Narrative review; predates cagrilintide / CagriSema clinical readouts.2010

PubMed3035556Westermark P et al. — Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells · Proceedings of the National Academy of Sciences USA · in-vitroIdentification of a neuropeptide-like protein as the precursor of islet amyloid in human insulinoma and feline diabetic islets - independent foundational characterisation of IAPP / amylin alongside Cooper 1987.Limitations: Structural / pathology paper; preclinical.1987

§ F · Safety signal

Pramlintide (the FDA-approved analog) carries a boxed warning for severe insulin-induced hypoglycaemia when added to mealtime insulin without insulin dose reduction. Nausea is the most common adverse effect of the amylin-analog class. Native amylin in research infusions has been associated with nausea and gastric stasis. The amyloidogenicity of the native peptide is a discovery / pathology concern, not a therapeutic-administration concern (since the native peptide is not administered).

§ H · Regulatory status

Regulatory status

FDA status:: Not FDA-approved

§ I · Notable gaps and controversies

The native peptide is not interchangeable with pramlintide or cagrilintide - the substitutions that make those analogs non-amyloidogenic are essential for drug-product feasibility. Vendor-sold 'amylin' research material does not interchange with the licensed pramlintide product (Symlin).

The amylin amyloid deposits seen in type 2 diabetes have been hypothesised to contribute to beta-cell failure; the causal contribution remains debated and is distinct from the receptor-pharmacology effects that drive the analog drug class.