Peptide YY (1-36)
Also known as: Full-length PYY, Peptide YY, PYY, PYY 1-36, PYY(1-36)
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Summary
Peptide YY (1-36) (PYY1-36) is a 36‑amino‑acid gut hormone that circulates in the bloodstream and acts on multiple Y‑type receptors (Y1, Y2, Y4, Y5). It influences gastrointestinal motility, pancreatic secretion, blood pressure, and appetite. Research has explored its role in diabetes, bariatric‑surgery outcomes, and cardiovascular physiology, but it remains an experimental compound without approved therapeutic use.
Mechanism of Action
PYY1-36 binds with high affinity to all four human Y‑receptors. Activation of Y1 and Y5 receptors in the hypothalamus stimulates appetite and can promote weight gain, while Y2 and Y4 receptors mediate inhibition of gastric acid secretion, gastric emptying, intestinal chloride secretion, and pancreatic exocrine activity. In pancreatic β‑cells, Y‑receptor signaling promotes proliferation and reduces apoptosis, enhancing insulin content. The peptide is normally cleaved by DPP‑4 to PYY3‑36, which loses Y1/Y5 activity and becomes a selective Y2 agonist that suppresses appetite.
What the Research Shows
Preclinical work with DPP‑4‑resistant, fish‑derived PYY1-36 peptides showed resistance to enzymatic degradation, inhibition of glucose‑stimulated insulin release, and strong β‑cell proliferative and anti‑apoptotic effects; in streptozotocin‑treated mice, sea‑lamprey PYY1-36 lowered non‑fasting glucose, glucagon, and fluid intake while improving glucose tolerance and islet morphology. Observational studies after bariatric surgery revealed that Roux‑en‑Y gastric bypass, but not sleeve gastrectomy, markedly increased post‑prandial PYY1-36 and PYY3-36 levels, suggesting a role in long‑term metabolic outcomes. Reviews describe PYY1-36’s broad receptor profile, its inhibition of gastrointestinal secretions, natriuretic and pressor actions, and its ability to cross the blood‑brain barrier. In vitro hypothalamic synaptosome assays, PYY1-36 did not alter dopamine, norepinephrine, or serotonin release, contrasting with PYY3-36. Context‑dependent concerns arise from DPP‑4 inhibitor studies, where elevated PYY1-36 may contribute to cardiac or renal injury under certain conditions.
Reported Benefits
Animal studies indicate that PYY1-36 can enhance pancreatic β‑cell survival, increase insulin content, and improve glycaemic control in diabetic models, pointing to potential antidiabetic applications. Post‑surgical hormone profiling suggests that elevated PYY1-36 after Roux‑en‑Y gastric bypass may support the procedure’s sustained metabolic benefits. Its ability to modulate gastrointestinal motility and secretion could be harnessed for disorders of gastric emptying or acid secretion, though evidence remains preclinical.
Limitations of the Evidence
Evidence for PYY1-36’s therapeutic effects is confined to rodent models and in vitro assays; no human interventional trials have been reported. Observational data after bariatric surgery describe hormone changes but do not prove causality. Potential cardiovascular and renal adverse effects are inferred from DPP‑4 inhibitor contexts rather than direct PYY1-36 administration. The peptide’s short half‑life and susceptibility to DPP‑4 cleavage (unless chemically stabilized) pose formulation challenges.
Safety Considerations
Preclinical data suggest PYY1-36 can raise systolic and diastolic blood pressure and promote natriuresis, indicating possible pressor effects. Context‑dependent studies of DPP‑4 inhibition raise concerns that elevated PYY1-36 may aggravate heart or kidney injury in certain disease states. Human safety, tolerability, and optimal dosing remain uncharacterized, and the peptide’s resistance to DPP‑4 degradation may alter its physiological profile. Caution is warranted until systematic toxicity assessments are completed.
How It Is Administered
In research settings PYY1-36 has been delivered by subcutaneous, intravenous, and intranasal routes as a synthetic peptide formulation. Studies typically use sterile aqueous solutions for injection or nasal spray; no oral or implantable formulations have been reported.
Routes of Administration
Goals & Uses
- Pancreatic exocrine secretion inhibitionGastrointestinalLow
- Obesity research biomarkerResearch / MetabolicModerate
- Type 2 diabetes adjunctMetabolicLow
- Obesity treatmentMetabolicModerate
- Gastrointestinal motility reduction (ileal brake)GastrointestinalModerate
- Appetite and satiety modulationMetabolic / EndocrineModerate
Contraindications
- Known hypersensitivity to PYY or excipientsImmunologicHigh
- Clinical therapeutic use outside approved trialsRegulatoryHigh
Adverse Effects
- Injection site reactionsLocalUncommon
- Reduced gastric motility / delayed gastric emptyingGastrointestinalCommon
- HypotensionCardiovascularUncommonLow blood pressure
- NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
- Abdominal painGastrointestinalUncommonPain or discomfort in the abdomen
Drug Interactions
- DPP-IV inhibitors (e.g., sitagliptin, saxagliptin)Moderate
- GLP‑1 receptor agonistsModerate
- Neuropeptide Y receptor antagonistsModerate
Population Constraints
- Pediatric populationsAgeRelative
- PediatricAgeRelative
- Patients with severe gastrointestinal dysmotilityGastrointestinalRelative
- Pregnant womenReproductiveRelative
Regulatory Status
- European UnionUnapprovedNo marketing authorization
- United StatesUnapprovedInvestigational use only
- United KingdomUnapprovedNo MHRA approval; utilized in academic and clinical research settings.
Not approved as a therapeutic agent; investigated in clinical trials for obesity and metabolic disorders.
Evidence & Sources
- Journal ArticleLowLafferty RA, et al.2020-01-01T00:00:00.000000Z
- Journal ArticleModerateJackson EK2017-01-01T00:00:00.000000Z
- Journal ArticleLowKowalka AM, et al.2023-01-01T00:00:00.000000Z
- Journal ArticleModerateBallantyne GH2006-01-01T00:00:00.000000Z
- Journal ArticleLowBrunetti L, et al.2005-01-01T00:00:00.000000Z
- Journal ArticleModerateBallantyne GH2006-01-01T00:00:00.000000Z
Frequently Asked Questions
What distinguishes PYY1-36 from PYY3-36?
PYY1-36 contains the full 36‑amino‑acid sequence and activates all four Y‑receptors (Y1, Y2, Y4, Y5), stimulating appetite and multiple gastrointestinal functions. DPP‑4 cleaves the N‑terminal two residues to generate PYY3-36, which is a selective Y2 agonist that suppresses appetite and promotes weight loss.
Has PYY1-36 been tested in humans for diabetes?
No human interventional trials have been published. The only efficacy data come from rodent models where DPP‑4‑resistant PYY1-36 improved β‑cell survival and glucose control. Human studies to date are limited to observational measurements of hormone levels after bariatric surgery.
Could PYY1-36 raise blood pressure?
Preclinical reports indicate that PYY1-36 can elevate systolic and diastolic blood pressure and increase natriuresis. Additionally, some analyses of DPP‑4 inhibitor effects suggest that higher circulating PYY1-36 might contribute to cardiovascular stress in certain contexts, although direct human evidence is lacking.
How is PYY1-36 administered in research?
Researchers have given synthetic PYY1-36 by subcutaneous injection, intravenous infusion, or intranasal spray, typically using sterile aqueous peptide solutions. The peptide is not formulated for oral use because it is rapidly degraded by gastrointestinal enzymes.
Why does PYY1-36 sometimes inhibit insulin secretion?
In vitro studies reported that PYY1-36 can suppress glucose‑stimulated insulin release, likely via Y‑receptor signaling that modulates β‑cell activity. However, in diabetic mouse models the same peptide also promoted β‑cell proliferation and reduced apoptosis, leading to net improvements in insulin content.
What is Peptide YY (1-36)?
Peptide YY (1-36) (PYY1-36) is a 36‑amino‑acid gut hormone that circulates in the bloodstream and acts on multiple Y‑type receptors (Y1, Y2, Y4, Y5). It influences gastrointestinal motility, pancreatic secretion, blood pressure, and appetite. Research has explored its role in diabetes, bariatric‑surgery outcomes, and cardiovascular physiology, but it remains an experimental compound without approved therapeutic use.
What is Peptide YY (1-36) used for?
Peptide YY (1-36) is educationally associated with: Pancreatic exocrine secretion inhibition, Obesity research biomarker, Type 2 diabetes adjunct, Obesity treatment, Gastrointestinal motility reduction (ileal brake), Appetite and satiety modulation. Educational only — not medical advice.
How is Peptide YY (1-36) administered?
Recorded routes of administration: Intranasal, Intravenous, Subcutaneous.
What are the potential side effects of Peptide YY (1-36)?
Reported adverse effects include: Injection site reactions, Reduced gastric motility / delayed gastric emptying, Hypotension, Nausea, Abdominal pain. This list is not exhaustive — consult a qualified clinician.
Who should avoid Peptide YY (1-36)?
Recorded contraindications: Known hypersensitivity to PYY or excipients, Clinical therapeutic use outside approved trials. Consult a qualified clinician before use.