Amylin
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Endogenous 37-amino acid pancreatic peptide co-secreted with insulin; promotes satiety, slows gastric emptying, suppresses glucagon. Template for pramlintide and cagrilintide.
Quick Facts
| Property | Value |
|---|---|
| Also Known As | IAPP (Islet Amyloid Polypeptide), Diabetes-Associated Peptide (DAP) |
| Category | Metabolic / Endogenous reference peptide |
| Sequence | KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY-NH₂ (37 aa; disulfide Cys2-Cys7; C-terminal amidation) |
| Molecular Weight | ~3906 Da |
| Molecular Formula | C₁₆₅H₂₆₁N₅₁O₅₅S₂ |
| PubChem CID | 70697771 |
| Administration | Not used therapeutically (analogs used instead) |
| Typical Dose Range | Not applicable — endogenous reference |
| Half-Life | ~15 minutes |
| Storage | Research-grade: lyophilized, -20 C (amyloidogenic — requires careful handling) |
| FDA Status | Not a drug product; endogenous hormone. FDA-approved analog: pramlintide (Symlin, 2005) |
| WADA Status | Not listed |
Mechanism of Action
Amylin (IAPP) is a 37-amino acid peptide hormone co-synthesized, co-packaged, and co-secreted with insulin from pancreatic beta cells at an approximate molar ratio of 1:100 (amylin:insulin). It was discovered in 1987 by Westermark et al. as the principal component of islet amyloid deposits in type 2 diabetes pancreata (PMID-21742788).
Amylin signals through the amylin receptor (AMY-R), which is a heteromeric complex of the calcitonin receptor (CTR) paired with receptor activity-modifying proteins (RAMP1, RAMP2, or RAMP3). This creates three receptor subtypes (AMY1-R, AMY2-R, AMY3-R) with different tissue distributions and signaling profiles (PMID-30919775).
Physiological functions:
- Satiety signaling — Amylin acts on the area postrema (AP) in the brainstem, a circumventricular organ outside the blood-brain barrier, to promote meal termination and reduce food intake. This is complementary to (not redundant with) leptin and GLP-1 satiety signals.
- Gastric emptying — Amylin slows gastric emptying, reducing the rate of nutrient delivery to the small intestine and smoothing postprandial glucose excursions.
- Glucagon suppression — Amylin inhibits postprandial glucagon secretion from alpha cells, preventing inappropriate hepatic glucose output after meals.
- Insulin complementarity — These three actions complement insulin's glucose-lowering effect, providing finer postprandial glucose control than insulin alone.
Pathological role: Human amylin is intrinsically amyloidogenic — residues 20-29 drive beta-sheet formation and fibril aggregation. Amyloid deposits are found in >90% of T2D pancreata and are cytotoxic to beta cells via membrane disruption and oxidative stress, contributing to progressive beta cell loss. Rat/mouse amylin has 3 proline substitutions that prevent aggregation — this insight led to the design of pramlintide (PMID-21742788).
Key Research Areas
- Beta cell biology — Amylin co-secretion with insulin, amyloid formation, and beta cell toxicity in T2D (PMID-21742788)
- Satiety and weight management — Amylin's central appetite-suppressing mechanism via area postrema (PMID-30919775)
- Amylin-leptin synergy — Combination produces greater weight loss than either alone; amylin may restore leptin sensitivity
- Pramlintide pharmacology — Non-amyloidogenic analog for T1D/T2D glucose control
- Cagrilintide development — Long-acting amylin analog for obesity (once-weekly dosing)
- CagriSema — Cagrilintide + semaglutide combination showing superior weight loss (~15-17%)
Evidence Level Summary
| Evidence Type | Count | Notes |
|---|---|---|
| Human RCTs | Many | For pramlintide (Symlin); Phase 2-3 for cagrilintide |
| Systematic reviews | Several | Pramlintide in T1D/T2D; amylin biology reviews |
| Human observational | Many | IAPP levels in T2D, obesity, anorexia nervosa |
| Animal in vivo | Extensive | Amylin physiology, amyloid models |
| In vitro | Extensive | Amyloid formation, receptor pharmacology |
Clinical Applications
- Weight Management — Amylin analog cagrilintide for weight loss
- Type 2 Diabetes — Amylin biology central to T2D pathophysiology
Protocols Using This Peptide
Amylin itself is not used in protocols. Its analogs are used for:
- Weight Loss Protocol — Via cagrilintide
- Metabolic Reset Protocol — Via pramlintide (insulin adjunct)
Ageless Peps Products
Amylin is an endogenous hormone and is NOT sold directly. The following Ageless Peps products are amylin analogs:
- Cagrilintide — Long-acting amylin analog (Cagrilintide Vial, WC ID 664)
Dosing Reference
Endogenous Levels
| Measurement | Value | Context |
|---|---|---|
| Fasting plasma | ~5-15 pmol/L | Healthy adults |
| Postprandial peak | ~15-30 pmol/L | Within 30-60 min of meal |
| T2D (early) | Elevated | Hyperinsulinemia drives IAPP hypersecretion |
| T2D (late) | Reduced | Beta cell loss reduces amylin and insulin |
Cycling
Not applicable — endogenous hormone with pulsatile secretion synchronized to insulin.
Contraindications & Safety
- Contraindications: Not applicable (endogenous hormone)
- Pathological significance: Human IAPP aggregation contributes to beta cell death in T2D
- Drug interactions: N/A for endogenous
- Pregnancy/nursing: Endogenous; plays role in fetal development
- Special populations: Reduced in late-stage T2D; elevated in insulin-resistant/pre-diabetic states
Synergistic Combinations
Understanding amylin's complementary mechanism explains clinical combinations:
- Amylin pathway (Cagrilintide) + GLP-1 pathway (Semaglutide) → CagriSema (complementary satiety pathways: AP + NTS/hypothalamus)
- Amylin + leptin → Synergistic weight loss (amylin restores leptin sensitivity)
- Amylin + insulin → Pramlintide (Symlin) as insulin adjunct in T1D/T2D
Related Research
| PMID | Title | Year | Study Type |
|---|---|---|---|
| 21742788 | IAPP, Islet Amyloid, and Diabetes Mellitus (Physiol Rev) | 2011 | Narrative Review |
| 30919775 | Human Amylin: From Pathology to Physiology and Pharmacology | 2019 | Narrative Review |
References
- PMID-21742788 — Westermark et al., IAPP and diabetes, Physiol Rev 2011
- PMID-30919775 — Hay et al., Amylin pharmacology and physiology, Pharmacol Rev 2019
Related
Educational Note: Amylin (IAPP) is an endogenous hormone included in this vault for educational purposes. Understanding amylin physiology is essential for comprehending the mechanism of pramlintide (Symlin) and cagrilintide, as well as the rationale for CagriSema combination therapy.
#peptide #metabolic #endogenous #not-sold