Apelin-13
Get a source-linked, educational explanation from this profile.
Complete Research Guide
Open each section for the available evidence. Gaps are stated rather than inferred.
Overview
Apelin-13 is listed as cardiometabolic / exerkine (apj receptor agonist).
- •Cardiovascular function research
- •Muscle aging (sarcopenia) research
- •Insulin sensitivity and glucose uptake research
- •Fluid balance (vasopressin counter-regulation)
- •Blood-vessel growth and maturation
- •Mitochondrial biogenesis in muscle
- •Kidney protection research
Regulatory status: Not FDA-approved for any use. Investigational research compound; sold as a research chemical. Not listed by name on the WADA prohibited list, but may fall under its general non-approved substances clause..
Structure & Properties
Compound: Apelin-13; also known as Apelin 13, [Pyr1]-Apelin-13, Pyr-apelin-13, APJ agonist peptide, APLNR ligand.
Pharmacologic class: Cardiometabolic / Exerkine (APJ receptor agonist).
Known delivery routes: IV Infusion (clinical research only), Subcutaneous (unstudied).
Sequence, molecular weight, salt form, and excipient details are formulation-specific and are not listed unless verified by a manufacturer or laboratory COA.
How It Works
A 13-amino-acid fragment of the endogenous hormone apelin and the dominant form in human plasma (as the pyroglutamate form, [Pyr1]-apelin-13). It activates the APJ receptor (APLNR), a G-protein-coupled receptor in heart, blood vessels, muscle, fat and kidney. Effects include nitric-oxide–dependent vasodilation, increased heart contractility without raising heart rate, AMPK activation that boosts glucose uptake and mitochondrial biogenesis in muscle, and suppression of vasopressin release. It is cleared within minutes in blood, largely by ACE2 and neprilysin.
- •Increased cardiac output and lower vascular resistance in short human infusion studies
- •Improves glucose uptake and insulin sensitivity in animal models
- •Reversed age-related muscle loss and improved muscle function in aged mice
- •Supports mitochondrial biogenesis in skeletal muscle (animal data)
- •Counteracts vasopressin, promoting water excretion (animal data)
- •Protective effects in animal models of kidney and heart injury
Human Research
Evidence grade: Clinical RCT (Limited)
Clinical RCT (Limited). Small human mechanistic studies (healthy volunteers and chronic heart failure patients) show short-term vasodilation and increased cardiac output. Extensive animal data in heart failure, insulin resistance, sarcopenia, kidney injury and angiogenesis. No long-term human safety or efficacy trials; longer-acting APJ agonists are in early drug development..
- Tatemoto K et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun. 1998;251:471-6.
- Lee DK et al. Characterization of apelin, the ligand for the APJ receptor. J Neurochem. 2000;74:34-41.
- Szokodi I et al. Apelin, the novel endogenous ligand of the orphan receptor APJ, is a potent cardiac inotrope. Circ Res. 2002;91:434-40.
- Japp AG et al. Vascular effects of apelin in vivo in man. J Am Coll Cardiol. 2008;52:908-13.
- Japp AG et al. Acute cardiovascular effects of apelin in humans: potential role in patients with chronic heart failure. Circulation. 2010;121:1818-27.
- Barnes GD et al. Sustained cardiovascular actions of APJ agonism during renin-angiotensin system activation and in patients with heart failure. Circ Heart Fail. 2013;6:482-91.
- Kuba K et al. Impaired heart contractility in apelin gene-deficient mice associated with aging and pressure overload. Circ Res. 2007;101:e32-42.
- Boucher J et al. Apelin, a newly identified adipokine up-regulated by insulin and obesity. Endocrinology. 2005;146:1764-71.
- Dray C et al. Apelin stimulates glucose utilization in normal and obese insulin-resistant mice. Cell Metab. 2008;8:437-45.
- Vinel C et al. The exerkine apelin reverses age-associated sarcopenia. Nat Med. 2018;24:1360-71.
- De Mota N et al. Apelin, a potent diuretic neuropeptide counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release. Proc Natl Acad Sci USA. 2004;101:10464-9.
- Kidoya H et al. Spatial and temporal role of the apelin/APJ system in the caliber size regulation of blood vessels during angiogenesis. EMBO J. 2008;27:522-34.
- Sorli SC et al. Apelin is a potent activator of tumour neoangiogenesis. Oncogene. 2007;26:7692-9.
- Wang W et al. Angiotensin-converting enzyme 2 metabolizes and partially inactivates pyr-apelin-13 and apelin-17: physiological effects in the cardiovascular system. Hypertension. 2016;68:365-77.
- Read C et al. International Union of Basic and Clinical Pharmacology. CVII. Structure and pharmacology of the apelin receptor with a recommendation that elabela/toddler is a second endogenous peptide ligand. Pharmacol Rev. 2019;71:467-502.
- Chapman FA et al. The therapeutic potential of apelin in kidney disease. Nat Rev Nephrol. 2021;17:840-53.
Laboratory Research
Small human mechanistic studies (healthy volunteers and chronic heart failure patients) show short-term vasodilation and increased cardiac output. Extensive animal data in heart failure, insulin resistance, sarcopenia, kidney injury and angiogenesis. No long-term human safety or efficacy trials; longer-acting APJ agonists are in early drug development.
Preclinical findings describe biological plausibility, not proven benefit in people. Animal and laboratory doses do not translate directly to human use.
Processing & Interactions
Timing and exposure
No established schedule. Human studies gave short supervised IV infusions only; the native peptide is cleared within minutes.
Potential interactions and combinations to avoid
- •Blood-pressure–lowering drugs or nitrates — additive hypotension
- •Active or suspected cancer — pro-angiogenic signaling
- •ACE2-modulating or neprilysin-inhibiting drugs (e.g., sacubitril) — may alter apelin breakdown
Absorption, half-life, metabolism, and clearance can vary by formulation and route. Use prescribing information when an approved product exists.
Safety & Precautions
Known or reported risks
- •Drop in blood pressure and reflex symptoms (flushing, light-headedness)
- •Pro-angiogenic activity — promotes tumor blood-vessel growth in animal studies
- •Extremely short half-life makes research-market injection effects unpredictable
- •No long-term human safety data
- •Research-chemical supply — purity, sterility and identity unverified
Contraindications
- •Active cancer or history of cancer (pro-angiogenic signaling)
- •Low blood pressure or use of blood-pressure–lowering medications
- •Pregnancy or breastfeeding
- •Proliferative diabetic retinopathy or other abnormal blood-vessel growth disorders
- •Under 18 years of age
- •Bleeding disorders or anticoagulant therapy without physician guidance (injection-site haematoma)
- •Active skin infection, cellulitis, or lipohypertrophy at intended injection sites
- •Inability to maintain sterile technique or safe sharps disposal
- •Not FDA-approved for human therapeutic use — no verified purity, sterility, or potency standards
- •Immunocompromised or transplant patients (unverified sterility and immunogenicity risk)
- •Concurrent participation in drug-tested sport (WADA prohibited or non-cleared substance)
- •Known hypersensitivity or prior reaction to this compound or any excipient/diluent
- •Pregnancy, attempting conception, or breastfeeding unless prescribed and monitored by a physician
- •Children and adolescents with open growth plates (unless under specialist endocrine care)
- •Active or recently treated malignancy without oncology clearance
- •Use without a confirmed diagnosis, baseline labs, and licensed clinical supervision
Unknown long-term toxicity should be assumed where controlled human data are limited. Seek urgent care for a severe or unexpected reaction.
Administration & Studied Formulations
Reference range: No established human dose. Human studies used brief intravenous or intra-arterial infusions only (e.g., 30–300 nmol/min for minutes); research-market subcutaneous dosing is unstudied.
Frequency: Not established — native peptide half-life is under ~5 minutes
Cycling: No evidence-based cycle exists. Human data are limited to single-session infusions lasting minutes to hours; any repeated use is outside studied conditions.
IV Infusion
Clinical research only — short supervised infusions with blood-pressure monitoring.
IV or intra-arterial infusion in a research setting. Clinician-only. No validated self-administration route or dose.
Subcutaneous research-market use has no human pharmacokinetic data; the native peptide is cleared within minutes.
Dosing information is educational context, not a personal recommendation. Approved products must follow their label and prescriber instructions.
Applications & Related Therapies
Potentially complementary measures
- •Regular aerobic and resistance exercise — naturally raises circulating apelin
- •Clinician-guided cardiometabolic care
Clinical use should account for diagnosis, approved alternatives, nutrition, activity, sleep, rehabilitation, current medicines, and appropriate monitoring.
Investigational only. Evidence is mainly mechanistic human infusion studies plus animal research; no human dosing protocol exists.
Cases, Considerations & Ethics
Decision framework: establish the clinical goal, confirm evidence quality and legal status, screen contraindications and interactions, compare approved alternatives, define monitoring and stopping criteria, and use shared decision-making with a licensed clinician.
Case evidence: individual reports cannot establish safety or effectiveness and should not outweigh controlled trials.
Ethics: informed consent should distinguish established care from experimental use, disclose uncertainty and cost, avoid overstated claims, and never substitute research products for medically necessary care.
What is Apelin-13?
In plain words
Apelin-13 is a short piece of a hormone the body naturally makes. It sends signals that can widen blood vessels, strengthen heart contractions and help muscles take in sugar, but the body breaks it down within minutes. Researchers study it for heart and blood-vessel function, age-related muscle loss and blood sugar control. Human trial evidence is limited, it can lower blood pressure, and there are no long-term human safety data.
Technical definition
Apelin-13 is a 13-amino-acid peptide fragment of the endogenous hormone apelin; its pyroglutamate form, [Pyr1]-apelin-13, is the dominant form in human plasma. It activates APJ (APLNR), a G-protein-coupled receptor in cardiovascular, muscle, fat and kidney tissues, promoting nitric-oxide–dependent vasodilation, increased cardiac contractility without increased heart rate, AMPK-mediated muscle glucose uptake and mitochondrial biogenesis, and suppression of vasopressin release; it is cleared within minutes, largely by ACE2 and neprilysin. It is an investigational research compound, not FDA-approved for any use; although not named on the WADA prohibited list, it may fall under the general non-approved substances clause.
Function
Dosing
Recommended Time of Day
Not established — human studies used brief supervised infusions; no time-of-day data.
See “Timing & Interactions” below for full fasted/fed circumstances, what to avoid combining, and what pairs well.
Administration & Technique
Injection & Application Sites
- IV — clinician only — Antecubital vein or central line. Not for home administration.
Diagram is a general illustration, not a medical instruction. Rotate sites every injection, keep 1 in (2.5 cm) between recent sites, and avoid scars, moles, bruises and the navel area.
Cycling
No evidence-based cycle exists. Human data are limited to single-session infusions lasting minutes to hours; any repeated use is outside studied conditions.
Timing & Interactions
- ·Blood-pressure–lowering drugs or nitrates — additive hypotension
- ·Active or suspected cancer — pro-angiogenic signaling
- ·ACE2-modulating or neprilysin-inhibiting drugs (e.g., sacubitril) — may alter apelin breakdown
- ·Regular aerobic and resistance exercise — naturally raises circulating apelin
- ·Clinician-guided cardiometabolic care
Storage & Reconstitution
Reconstitution Calculator
1 mL = 100 units on a standard U-100 insulin syringe. Draw to the nearest 0.5 unit and confirm dosing with a clinician before injection.
Your Notes
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Benefits
- ·Increased cardiac output and lower vascular resistance in short human infusion studies
- ·Improves glucose uptake and insulin sensitivity in animal models
- ·Reversed age-related muscle loss and improved muscle function in aged mice
- ·Supports mitochondrial biogenesis in skeletal muscle (animal data)
- ·Counteracts vasopressin, promoting water excretion (animal data)
- ·Protective effects in animal models of kidney and heart injury
Risks
- ·Drop in blood pressure and reflex symptoms (flushing, light-headedness)
- ·Pro-angiogenic activity — promotes tumor blood-vessel growth in animal studies
- ·Extremely short half-life makes research-market injection effects unpredictable
- ·No long-term human safety data
- ·Research-chemical supply — purity, sterility and identity unverified
Contraindications
- ·Active cancer or history of cancer (pro-angiogenic signaling)
- ·Low blood pressure or use of blood-pressure–lowering medications
- ·Pregnancy or breastfeeding
- ·Proliferative diabetic retinopathy or other abnormal blood-vessel growth disorders
- ·Under 18 years of age
- ·Bleeding disorders or anticoagulant therapy without physician guidance (injection-site haematoma)
- ·Active skin infection, cellulitis, or lipohypertrophy at intended injection sites
- ·Inability to maintain sterile technique or safe sharps disposal
- ·Not FDA-approved for human therapeutic use — no verified purity, sterility, or potency standards
- ·Immunocompromised or transplant patients (unverified sterility and immunogenicity risk)
- ·Concurrent participation in drug-tested sport (WADA prohibited or non-cleared substance)
- ·Known hypersensitivity or prior reaction to this compound or any excipient/diluent
- ·Pregnancy, attempting conception, or breastfeeding unless prescribed and monitored by a physician
- ·Children and adolescents with open growth plates (unless under specialist endocrine care)
- ·Active or recently treated malignancy without oncology clearance
- ·Use without a confirmed diagnosis, baseline labs, and licensed clinical supervision
Regulatory
Not FDA-approved for any use. Investigational research compound; sold as a research chemical. Not listed by name on the WADA prohibited list, but may fall under its general non-approved substances clause.
Veterinary Use (Pets)
No established veterinary protocol for Apelin-13. Consult a licensed veterinarian before considering off-label use in any species.
Full veterinary reference →Functional Groups
Cited Works
Tap any study to open the published work.
- 1.Tatemoto K et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun. 1998;251:471-6.Read published work Link not opening? Search Google Scholar
- 2.Lee DK et al. Characterization of apelin, the ligand for the APJ receptor. J Neurochem. 2000;74:34-41.Read published work Link not opening? Search Google Scholar
- 3.Szokodi I et al. Apelin, the novel endogenous ligand of the orphan receptor APJ, is a potent cardiac inotrope. Circ Res. 2002;91:434-40.Read published work Link not opening? Search Google Scholar
- 4.Japp AG et al. Vascular effects of apelin in vivo in man. J Am Coll Cardiol. 2008;52:908-13.Read published work Link not opening? Search Google Scholar
- 5.Japp AG et al. Acute cardiovascular effects of apelin in humans: potential role in patients with chronic heart failure. Circulation. 2010;121:1818-27.Read published work Link not opening? Search Google Scholar
- 6.Barnes GD et al. Sustained cardiovascular actions of APJ agonism during renin-angiotensin system activation and in patients with heart failure. Circ Heart Fail. 2013;6:482-91.Read published work Link not opening? Search Google Scholar
- 7.Kuba K et al. Impaired heart contractility in apelin gene-deficient mice associated with aging and pressure overload. Circ Res. 2007;101:e32-42.Read published work Link not opening? Search Google Scholar
- 8.Boucher J et al. Apelin, a newly identified adipokine up-regulated by insulin and obesity. Endocrinology. 2005;146:1764-71.Read published work Link not opening? Search Google Scholar
- 9.Dray C et al. Apelin stimulates glucose utilization in normal and obese insulin-resistant mice. Cell Metab. 2008;8:437-45.Read published work Link not opening? Search Google Scholar
- 10.Vinel C et al. The exerkine apelin reverses age-associated sarcopenia. Nat Med. 2018;24:1360-71.Read published work Link not opening? Search Google Scholar
- 11.De Mota N et al. Apelin, a potent diuretic neuropeptide counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release. Proc Natl Acad Sci USA. 2004;101:10464-9.Read published work Link not opening? Search Google Scholar
- 12.Kidoya H et al. Spatial and temporal role of the apelin/APJ system in the caliber size regulation of blood vessels during angiogenesis. EMBO J. 2008;27:522-34.Read published work Link not opening? Search Google Scholar
- 13.Sorli SC et al. Apelin is a potent activator of tumour neoangiogenesis. Oncogene. 2007;26:7692-9.Read published work Link not opening? Search Google Scholar
- 14.Wang W et al. Angiotensin-converting enzyme 2 metabolizes and partially inactivates pyr-apelin-13 and apelin-17: physiological effects in the cardiovascular system. Hypertension. 2016;68:365-77.Read published work Link not opening? Search Google Scholar
- 15.Read C et al. International Union of Basic and Clinical Pharmacology. CVII. Structure and pharmacology of the apelin receptor with a recommendation that elabela/toddler is a second endogenous peptide ligand. Pharmacol Rev. 2019;71:467-502.Read published work Link not opening? Search Google Scholar
- 16.Chapman FA et al. The therapeutic potential of apelin in kidney disease. Nat Rev Nephrol. 2021;17:840-53.Read published work Link not opening? Search Google Scholar
