Side-by-side · Research reference
GLP-1 (7-37)vsPE 22-28
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AHuman-MechanisticHUMAN-REVIEWED16/43 cited
BAnimal-StrongHUMAN-REVIEWED16/47 cited
GLP-1 (7-37)
Incretin Hormone · Native Peptide
Research use only · IV/SC in experimental settings
PE 22-28
TREK-1 Antagonist · Pre-Clinical
IP · SQ · Once Daily (animal models)Djillani 2017Pietri 2019
01Mechanism of Action
Parameter
GLP-1 (7-37)
PE 22-28
Primary target
GLP-1 receptor (class B GPCR)Koole 2015
TREK-1 two-pore-domain potassium channelDjillani 2017Ma 2020
Pathway
GLP-1R activation → cAMP production → PKA signaling → insulin secretion (pancreatic β-cells)Lu 2025Koole 2015
TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity
Downstream effect
Glucose-dependent insulin release, glucagon suppression, delayed gastric emptying, reduced food intakeLu 2025Ding 2017
Antidepressant-like activity in forced swim test and tail suspension test; reduced A1-like reactive astrocyte activation; neuroprotection via NF-κB pathway modulationDjillani 2017Cong 2023Wu 2021
Feedback intact?
Yes — physiological secretion and degradation preserved
N/A — direct ion channel blockade; not receptor-mediated endocrine axis
Origin
Endogenous peptide cleaved from proglucagon in intestinal L cells; secreted postprandially
Synthetic truncation of spadin (PE 12-28), itself derived from the sortilin propeptide C-terminus. Residues 22-28: Val-Val-Arg-Gly-Trp-Leu-Arg.Djillani 2017Mazella 2018
Antibody development
—
Not reported in animal studies
02Dosage Protocols
Parameter
GLP-1 (7-37)
PE 22-28
Clinical use
None — native GLP-1 not used therapeutically
Engineered analogues (semaglutide, liraglutide) used clinically.Friedman 2024
—
Research dosing
Variable — 0.1–10 nmol/kg in animal models
Used as reference standard for analogue comparison.
—
Modified analogues
t½ extended to 13 h (liraglutide), 165 h (semaglutide)
Via DPP-4 resistance + fatty acid acylation.
—
Animal dose (antidepressant)
—
0.3–3 µg/kg IP
Effective in forced swim test, tail suspension test, CUMS models.
Animal dose (neuroprotection)
—
0.03 µg/kg IPPietri 2019
Low-dose TREK-1 activation post-stroke for 7 days, then high-dose blockade.
Frequency
—
Once daily
Sustained antidepressant effect over 7+ days.
Onset (animal)
—
Within hours (acute); full effect 4–7 days
Comparison to fluoxetine
—
PE 22-28 outperforms fluoxetine in CUMS-sensitive rats by day 7
Chronic administration shows superior long-term efficacy.
Human equivalent (extrapolated)
—
Not established — no clinical trials
Allometric scaling from rodent data unavailable.
Evidence basis
—
Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017Qi 2018Wu 2021
03Metabolic / Fat Loss Evidence
Parameter
GLP-1 (7-37)
PE 22-28
Mechanism
GLP-1R activation in hypothalamic satiety centers (arcuate nucleus) reduces food intakeLu 2025
Effect demonstrated with long-acting analogues (liraglutide).Lu 2025
—
Native GLP-1 efficacy
Minimal — rapid degradation prevents sustained appetite suppression
—
Gastric emptying
Delayed in animal models, contributing to satiety
—
Body weight impact
Not observed with native GLP-1 — requires analogue formulations
—
04Side Effects & Safety
Parameter
GLP-1 (7-37)
PE 22-28
Native GLP-1
Well-tolerated in research settings; no prolonged exposure data
—
Hypoglycemia risk
Low — insulin secretion is glucose-dependent
—
Analogue side effects
Nausea, vomiting, diarrhea (GLP-1R agonists)
Not applicable to native GLP-1 due to non-therapeutic use.
—
GLP-1 resistance
High glucose-induced PKCβ overexpression may reduce GLP-1 responsiveness in endothelial cellsPujadas 2016
—
Toxicity (animal)
—
No adverse effects reported at therapeutic doses
Cardiovascular (theoretical)
—
TREK-1 expressed in cardiac tissue; arrhythmia risk unclear
Weight change
—
Not reported in animal studies
Neurological
—
No seizures or behavioral abnormalities noted
Long-term safety
—
Unknown — longest animal study 28 days
Absolute Contraindications
GLP-1 (7-37)
—PE 22-28
- ·Human use — no clinical safety data available
Relative Contraindications
GLP-1 (7-37)
—PE 22-28
- ·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)
05Administration Protocol
Parameter
GLP-1 (7-37)
PE 22-28
1. Research use only
Native GLP-1(7-37) is not formulated for therapeutic use. Administered IV or SC in experimental protocols to study GLP-1R pharmacology and as reference standard for analogue development.
Dissolved in sterile saline or vehicle. Intraperitoneal injection, 0.3–3 µg/kg body weight. Once daily administration in rodent behavioral studies.
2. Storage
Lyophilised peptide stored at -20°C or below. Reconstituted solutions should be prepared fresh and used immediately due to rapid degradation.
Shorter peptide length (7 AA) confers improved plasma stability vs 17-AA spadin. Exact storage conditions not detailed in published protocols.Djillani 2017
3. Clinical alternatives
For therapeutic GLP-1R activation, use FDA-approved long-acting analogues: semaglutide (once weekly), liraglutide (once daily), dulaglutide (once weekly), or exenatide (twice daily or once weekly).
Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.
4. Human formulation
—
Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.